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by blocking replication will tend to cause replication errors and thus mutation. The great majority of mutations that are not neutral in their effect are deleterious to a cell's survival. Thus, in a population of cells composing a tissue with replicating cells, mutant cells will tend to be lost. However, infrequent mutations that provide a survival advantage will tend to clonally expand at the expense of neighboring cells in the tissue. This advantage to the cell is disadvantageous to the whole organism because such mutant cells can give rise to cancer. Thus, DNA damage in frequently dividing cells, because it gives rise to mutations, is a prominent cause of cancer. In contrast, DNA damage in infrequently-dividing cells is likely a prominent cause of aging.
2535:
2976:(NHEJ) repair of a double-strand break can cause a small number of demethylations of pre-existing cytosine DNA methylations downstream of the repaired double-strand break. Further work by Allen et al. showed that NHEJ of a DNA double-strand break in a cell could give rise to some progeny cells having repressed expression of the gene harboring the initial double-strand break and some progeny having high expression of that gene due to epigenetic alterations associated with NHEJ repair. The frequency of epigenetic alterations causing repression of a gene after an NHEJ repair of a DNA double-strand break in that gene may be about 0.9%.
920:, directly joins the two ends. To guide accurate repair, NHEJ relies on short homologous sequences called microhomologies present on the single-stranded tails of the DNA ends to be joined. If these overhangs are compatible, repair is usually accurate. NHEJ can also introduce mutations during repair. Loss of damaged nucleotides at the break site can lead to deletions, and joining of nonmatching termini forms insertions or translocations. NHEJ is especially important before the cell has replicated its DNA, since there is no template available for repair by homologous recombination. There are "backup" NHEJ pathways in higher
1590:
permits differential binding of LexA to different promoters and allows for timing of the SOS response. The lesion repair genes are induced at the beginning of SOS response. The error-prone translesion polymerases, for example, UmuCD'2 (also called DNA polymerase V), are induced later on as a last resort. Once the DNA damage is repaired or bypassed using polymerases or through recombination, the amount of single-stranded DNA in cells is decreased, lowering the amounts of RecA filaments decreases cleavage activity of LexA homodimer, which then binds to the SOS boxes near promoters and restores normal gene expression.
2773:
2961:
break. When the chromosome is replicated, this gives rise to one daughter chromosome that is heavily methylated downstream of the previous break site and one that is unmethylated in the region both upstream and downstream of the previous break site. With respect to the gene that was broken by the double-strand break, half of the progeny cells express that gene at a high level and in the other half of the progeny cells expression of that gene is repressed. When clones of these cells were maintained for three years, the new methylation patterns were maintained over that time period.
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1926:
the gut, skin, and hematopoietic system are also affected. Modern cancer treatments attempt to localize the DNA damage to cells and tissues only associated with cancer, either by physical means (concentrating the therapeutic agent in the region of the tumor) or by biochemical means (exploiting a feature unique to cancer cells in the body). In the context of therapies targeting DNA damage response genes, the latter approach has been termed 'synthetic lethality'.
10662:
3086:-Cas9) was discovered in 2012. The new technology allows anyone with molecular biology training to alter the genes of any species with precision, by inducing DNA damage at a specific point and then altering DNA repair mechanisms to insert new genes. It is cheaper, more efficient, and more precise than other technologies. With the help of CRISPR–Cas9, parts of a genome can be edited by scientists by removing, adding, or altering parts in a DNA sequence.
1638:, global transcriptional activation, genes controlling mRNA decay, and many others. A large amount of damage to a cell leaves it with an important decision: undergo apoptosis and die, or survive at the cost of living with a modified genome. An increase in tolerance to damage can lead to an increased rate of survival that will allow a greater accumulation of mutations. Yeast Rev1 and human polymerase η are members of Y family translesion DNA
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9999:
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regulation and by recombination and selection of alleles. On the other hand, DNA damage repair and protection does influence the rate of accumulation of irreparable, advantageous, code expanding, inheritable mutations, and slows down the evolutionary mechanism for expansion of the genome of organisms with new functionalities. The tension between evolvability and mutation repair and protection needs further investigation.
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1148:. Pol ζ is unique in that it can extend terminal mismatches, whereas more processive polymerases cannot. So when a lesion is encountered, the replication fork will stall, PCNA will switch from a processive polymerase to a TLS polymerase such as Pol ι to fix the lesion, then PCNA may switch to Pol ζ to extend the mismatch, and last PCNA will switch to the processive polymerase to continue replication.
1771:, can significantly extend lifespan. The mammalian homolog of SIR-2 is known to induce downstream DNA repair factors involved in NHEJ, an activity that is especially promoted under conditions of caloric restriction. Caloric restriction has been closely linked to the rate of base excision repair in the nuclear DNA of rodents, although similar effects have not been observed in mitochondrial DNA.
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2816:(OGG1) is the primary enzyme responsible for the excision of the oxidized guanine during DNA repair. OGG1 finds and binds to an 8-OHdG within a few seconds. However, OGG1 does not immediately excise 8-OHdG. In HeLa cells half maximum removal of 8-OHdG occurs in 30 minutes, and in irradiated mice, the 8-OHdGs induced in the mouse liver are removed with a half-life of 11 minutes.
880:. In fact, when a double-strand break is accompanied by a cross-linkage joining the two strands at the same point, neither strand can be used as a template for the repair mechanisms, so that the cell will not be able to complete mitosis when it next divides, and will either die or, in rare cases, undergo a mutation. Three mechanisms exist to repair double-strand breaks (DSBs):
1746:. The molecular mechanisms by which such restriction results in lengthened lifespan are as yet unclear (see for some discussion); however, the behavior of many genes known to be involved in DNA repair is altered under conditions of caloric restriction. Several agents reported to have anti-aging properties have been shown to attenuate constitutive level of
147:
704:(but cells remain superficially functional when non-essential genes are missing or damaged). Depending on the type of damage inflicted on the DNA's double helical structure, a variety of repair strategies have evolved to restore lost information. If possible, cells use the unmodified complementary strand of the DNA or the sister
859:, the proteins involved are the Mut class proteins: MutS, MutL, and MutH. In most Eukaryotes, the analog for MutS is MSH and the analog for MutL is MLH. MutH is only present in bacteria. This is followed by removal of damaged region by an exonuclease, resynthesis by DNA polymerase, and nick sealing by DNA ligase.
652:). Senescence in cells may serve as a functional alternative to apoptosis in cases where the physical presence of a cell for spatial reasons is required by the organism, which serves as a "last resort" mechanism to prevent a cell with damaged DNA from replicating inappropriately in the absence of pro-growth
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repair pathway for double-strand breaks. In MMEJ repair of a double-strand break, an homology of 5–25 complementary base pairs between both paired strands is sufficient to align the strands, but mismatched ends (flaps) are usually present. MMEJ removes the extra nucleotides (flaps) where strands are
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The chart in this section shows some frequent DNA damaging agents, examples of DNA lesions they cause, and the pathways that deal with these DNA damages. At least 169 enzymes are either directly employed in DNA repair or influence DNA repair processes. Of these, 83 are directly employed in repairing
2543:
Deficiencies in DNA repair enzymes are occasionally caused by a newly arising somatic mutation in a DNA repair gene, but are much more frequently caused by epigenetic alterations that reduce or silence expression of DNA repair genes. For example, when 113 colorectal cancers were examined in sequence,
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While large numbers of epigenetic alterations are found in cancers, the epigenetic alterations in DNA repair genes, causing reduced expression of DNA repair proteins, appear to be particularly important. Such alterations are thought to occur early in progression to cancer and to be a likely cause of
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indicates that a general global stress response pathway exist at the level of transcriptional activation. In contrast, different human cell types respond to damage differently indicating an absence of a common global response. The probable explanation for this difference between yeast and human cells
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to provide a platform for the specialized polymerases to bypass the lesion and resume DNA replication. After translesion synthesis, extension is required. This extension can be carried out by a replicative polymerase if the TLS is error-free, as in the case of Pol η, yet if TLS results in a mismatch,
1118:
either bypassing or repairing lesions at locations of stalled DNA replication. For example, Human DNA polymerase eta can bypass complex DNA lesions like guanine-thymine intra-strand crosslink, GT, although it can cause targeted and semi-targeted mutations. Paromita
Raychaudhury and Ashis Basu studied
724:
Cells are known to eliminate three types of damage to their DNA by chemically reversing it. These mechanisms do not require a template, since the types of damage they counteract can occur in only one of the four bases. Such direct reversal mechanisms are specific to the type of damage incurred and do
2538:
A chart of common DNA damaging agents, examples of lesions they cause in DNA, and pathways used to repair these lesions. Also shown are many of the genes in these pathways, an indication of which genes are epigenetically regulated to have reduced (or increased) expression in various cancers. It also
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Many other drugs for use against other residual DNA repair mechanisms commonly found in cancer are currently under investigation. However, synthetic lethality therapeutic approaches have been questioned due to emerging evidence of acquired resistance, achieved through rewiring of DNA damage response
1945:
is combined with chemotherapeutics to inhibit single-strand break repair induced by DNA damage caused by the co-administered chemotherapy. Tumor cells relying on this residual DNA repair mechanism are unable to repair the damage and hence are not able to survive and proliferate, whereas normal cells
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and infections more often, and, as a consequence, have shorter lifespans than wild-type mice. In similar manner, mice deficient in a key repair and transcription protein that unwinds DNA helices have premature onset of aging-related diseases and consequent shortening of lifespan. However, not every
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variant H2AX constitutes about 10% of the H2A histones in human chromatin. γH2AX (H2AX phosphorylated on serine 139) can be detected as soon as 20 seconds after irradiation of cells (with DNA double-strand break formation), and half maximum accumulation of γH2AX occurs in one minute. The extent of
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with specific DNA polymerase knockouts. Viability was very low in a strain lacking pol II, pol IV, and pol V, the three SOS-inducible DNA polymerases, indicating that translesion synthesis is conducted primarily by these specialized DNA polymerases. A bypass platform is provided to these polymerases
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Another type of DNA double-strand breaks originates from the DNA heat-sensitive or heat-labile sites. These DNA sites are not initial DSBs. However, they convert to DSB after treating with elevated temperature. Ionizing irradiation can induces a highly complex form of DNA damage as clustered damage.
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Damage to DNA alters the spatial configuration of the helix, and such alterations can be detected by the cell. Once damage is localized, specific DNA repair molecules bind at or near the site of damage, inducing other molecules to bind and form a complex that enables the actual repair to take place.
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gene. Oxidative DNA damage from bromate modulated the DNA methylation pattern (caused epigenetic alterations) at CpG sites within the region of DNA studied. In untreated cells, CpGs located at −189, −134, −29, −19, +16, and +19 of the BRCA1 gene had methylated cytosines (where numbering is from the
1967:
Replication stress, along with the selection for inactivating mutations in DNA damage response genes in the evolution of the tumor, leads to downregulation and/or loss of some DNA damage response mechanisms, and hence loss of DNA repair and/or senescence/programmed cell death. In experimental mouse
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It has become apparent over the past several years that the DNA damage response acts as a barrier to the malignant transformation of preneoplastic cells. Previous studies have shown an elevated DNA damage response in cell-culture models with oncogene activation and preneoplastic colon adenomas. DNA
1925:
work by overwhelming the capacity of the cell to repair DNA damage, resulting in cell death. Cells that are most rapidly dividing – most typically cancer cells – are preferentially affected. The side-effect is that other non-cancerous but rapidly dividing cells such as progenitor cells in
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activity, which ultimately leads to cleavage of LexA dimer and subsequent LexA degradation. The loss of LexA repressor induces transcription of the SOS genes and allows for further signal induction, inhibition of cell division and an increase in levels of proteins responsible for damage processing.
685:
Given these properties of DNA damage and mutation, it can be seen that DNA damage is a special problem in non-dividing or slowly-dividing cells, where unrepaired damage will tend to accumulate over time. On the other hand, in rapidly dividing cells, unrepaired DNA damage that does not kill the cell
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A certain irreducible background incidence of cancer is to be expected regardless of circumstances: mutations can never be absolutely avoided, because they are an inescapable consequence of fundamental limitations on the accuracy of DNA replication, as discussed in
Chapter 5. If a human could live
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Damage to DNA is very common and is constantly being repaired. Epigenetic alterations can accompany DNA repair of oxidative damage or double-strand breaks. In human cells, oxidative DNA damage occurs about 10,000 times a day and DNA double-strand breaks occur about 10 to 50 times a cell cycle in
673:
residues, and polycyclic aromatic hydrocarbon adducts. DNA damage can be recognized by enzymes, and thus can be correctly repaired if redundant information, such as the undamaged sequence in the complementary DNA strand or in a homologous chromosome, is available for copying. If a cell retains DNA
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downstream of the repaired double-strand break. The other DNA strand loses methylation at about six CpG sites that were previously methylated downstream of the double-strand break, as well as losing methylation at about five CpG sites that were previously methylated upstream of the double-strand
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structure and a high degree of sequence conservation. In other classes and phyla, the sequence of SOS boxes varies considerably, with different length and composition, but it is always highly conserved and one of the strongest short signals in the genome. The high information content of SOS boxes
677:
In contrast to DNA damage, a mutation is a change in the base sequence of the DNA. A mutation cannot be recognized by enzymes once the base change is present in both DNA strands, and thus a mutation cannot be repaired. At the cellular level, mutations can cause alterations in protein function and
3073:
in a particular species (or, in a particular gene) is a function of the rate of mutation. As a consequence, the rate and accuracy of DNA repair mechanisms have an influence over the process of evolutionary change. DNA damage protection and repair does not influence the rate of adaptation by gene
2589:
Some of the more well studied genes central to these repair processes are shown in the chart. The gene designations shown in red, gray or cyan indicate genes frequently epigenetically altered in various types of cancers. Knowledge articles on each of the genes highlighted by red, gray or cyan
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are respectively ~3, ~30 and ~129 years. Of these, the shortest lived species, mouse, expresses DNA repair genes, including core genes in several DNA repair pathways, at a lower level than do humans and naked mole rats. Furthermore several DNA repair pathways in humans and naked mole-rats are
2502:
Reduced expression of DNA repair genes causes deficient DNA repair. When DNA repair is deficient DNA damages remain in cells at a higher than usual level and these excess damages cause increased frequencies of mutation or epimutation. Mutation rates increase substantially in cells defective in
1983:
The prevalence of DNA damage response mutations differs across cancer types; for example, 30% of breast invasive carcinomas have mutations in genes involved in homologous recombination. In cancer, downregulation is observed across all DNA damage response mechanisms (base excision repair (BER),
1702:
If the rate of DNA damage exceeds the capacity of the cell to repair it, the accumulation of errors can overwhelm the cell and result in early senescence, apoptosis, or cancer. Inherited diseases associated with faulty DNA repair functioning result in premature aging, increased sensitivity to
1262:
quickly attaches to the product of PARP1 action, a poly-ADP ribose chain, and ALC1 completes arrival at the DNA damage within 10 seconds of the occurrence of the damage. About half of the maximum chromatin relaxation, presumably due to action of ALC1, occurs by 10 seconds. This then allows
2709:
Differential activity of DNA repair pathways across various regions of the human genome causes mutations to be very unevenly distributed within tumor genomes. In particular, the gene-rich, early-replicating regions of the human genome exhibit lower mutation frequencies than the gene-poor,
588:. Whenever a cell needs to express the genetic information encoded in its n-DNA the required chromosomal region is unraveled, genes located therein are expressed, and then the region is condensed back to its resting conformation. Mitochondrial DNA (mtDNA) is located inside mitochondria
1076:
for specialized translesion polymerases (i.e. DNA polymerase IV or V, from the Y Polymerase family), often with larger active sites that can facilitate the insertion of bases opposite damaged nucleotides. The polymerase switching is thought to be mediated by, among other factors, the
2444:
Genes involved in DNA damage response pathways and frequently mutated in cancer (HR = homologous recombination; NHEJ = non-homologous end joining; SSA = single-strand annealing; FA = fanconi anemia pathway; BER = base excision repair; NER = nucleotide excision repair; MMR = mismatch
1984:
nucleotide excision repair (NER), DNA mismatch repair (MMR), homologous recombination repair (HR), non-homologous end joining (NHEJ) and translesion DNA synthesis (TLS). As well as mutations to DNA damage repair genes, mutations also arise in the genes responsible for arresting the
2552:, while the majority had reduced MGMT expression due to methylation of the MGMT promoter region (an epigenetic alteration). Five different studies found that between 40% and 90% of colorectal cancers have reduced MGMT expression due to methylation of the MGMT promoter region.
1988:
to allow sufficient time for DNA repair to occur, and some genes are involved in both DNA damage repair and cell cycle checkpoint control, for example ATM and checkpoint kinase 2 (CHEK2) – a tumor suppressor that is often absent or downregulated in non-small cell lung cancer.
5954:
MacRae SL, Croken MM, Calder RB, Aliper A, Milholland B, White RR, Zhavoronkov A, Gladyshev VN, Seluanov A, Gorbunova V, Zhang ZD, Vijg J (2015). "DNA repair in species with extreme lifespan differences". Aging. 7 (12): 1171–84. doi:10.18632/aging.100866. PMC 4712340.
107:
The rate of DNA repair depends on various factors, including the cell type, the age of the cell, and the extracellular environment. A cell that has accumulated a large amount of DNA damage or can no longer effectively repair its DNA may enter one of three possible states:
1085:. Translesion synthesis polymerases often have low fidelity (high propensity to insert wrong bases) on undamaged templates relative to regular polymerases. However, many are extremely efficient at inserting correct bases opposite specific types of damage. For example,
1959:
damage response mechanisms trigger cell-cycle arrest, and attempt to repair DNA lesions or promote cell death/senescence if repair is not possible. Replication stress is observed in preneoplastic cells due to increased proliferation signals from oncogenic mutations.
2455:
Classically, cancer has been viewed as a set of diseases that are driven by progressive genetic abnormalities that include mutations in tumour-suppressor genes and oncogenes, and chromosomal aberrations. However, it has become apparent that cancer is also driven by
343:
The replication of damaged DNA before cell division can lead to the incorporation of wrong bases opposite damaged ones. Daughter cells that inherit these wrong bases carry mutations from which the original DNA sequence is unrecoverable (except in the rare case of a
2685:, the flap endonuclease in MMEJ, is epigenetically increased by promoter hypomethylation and is over-expressed in the majority of cancers of the breast, prostate, stomach, neuroblastomas, pancreas, and lung. PARP1 is also over-expressed when its promoter region
1052:
It consists of different types of DNA lesions in various locations of the DNA helix. Some of these closely located lesions can probably convert to DSB by exposure to high temperatures. But the exact nature of these lesions and their interactions is not yet known
3028:
became the sole and universal means of encoding genetic information, requiring DNA repair mechanisms that in their basic form have been inherited by all extant life forms from their common ancestor. The emergence of Earth's oxygen-rich atmosphere (known as the
2894:
for 30 minutes causes the mismatch repair protein heterodimer MSH2-MSH6 to recruit DNA methyltransferase 1 (DNMT1) to sites of some kinds of oxidative DNA damage. This could cause increased methylation of cytosines (epigenetic alterations) at these locations.
1048:, which is especially common in regions near an open replication fork. Such breaks are not considered DNA damage because they are a natural intermediate in the topoisomerase biochemical mechanism and are immediately repaired by the enzymes that created them.
7880:
Mokarram P, Zamani M, Kavousipour S, Naghibalhossaini F, Irajie C, Moradi Sarabi M, et al. (May 2013). "Different patterns of DNA methylation of the two distinct O6-methylguanine-DNA methyltransferase (O6-MGMT) promoter regions in colorectal cancer".
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the damaged DNA backbone at the AP site. DNA polymerase then removes the damaged region using its 5' to 3' exonuclease activity and correctly synthesizes the new strand using the complementary strand as a template. The gap is then sealed by enzyme DNA
150:
201:
processes inside the cell, occurs at a rate of 10,000 to 1,000,000 molecular lesions per cell per day. While this constitutes at most only 0.0003125% of the human genome's approximately 3.2 billion bases, unrepaired lesions in critical genes (such as
2514:
Higher levels of DNA damage not only cause increased mutation, but also cause increased epimutation. During repair of DNA double strand breaks, or repair of other DNA damages, incompletely cleared sites of repair can cause epigenetic gene silencing.
149:
668:
It is important to distinguish between DNA damage and mutation, the two major types of error in DNA. DNA damage and mutation are fundamentally different. Damage results in physical abnormalities in the DNA, such as single- and double-strand breaks,
154:
153:
148:
799:
When only one of the two strands of a double helix has a defect, the other strand can be used as a template to guide the correction of the damaged strand. In order to repair damage to one of the two paired molecules of DNA, there exist a number of
2758:(8-OHdG) in the average mammalian cell DNA. 8-OHdG constitutes about 5% of the oxidative damages commonly present in DNA. The oxidized guanines do not occur randomly among all guanines in DNA. There is a sequence preference for the guanine at a
2939:
region). Bromate treatment-induced oxidation resulted in the loss of cytosine methylation at −189, −134, +16 and +19 while also leading to the formation of new methylation at the CpGs located at −80, −55, −21 and +8 after DNA repair was allowed.
1778:
gene AGE-1, an upstream effector of DNA repair pathways, confers dramatically extended life span under free-feeding conditions but leads to a decrease in reproductive fitness under conditions of caloric restriction. This observation supports the
1188:, are among known stimulation signals for a global response to DNA damage. The global response to damage is an act directed toward the cells' own preservation and triggers multiple pathways of macromolecular repair, lesion bypass, tolerance, or
487:
causes breaks in DNA strands. Intermediate-level ionizing radiation may induce irreparable DNA damage (leading to replicational and transcriptional errors needed for neoplasia or may trigger viral interactions) leading to pre-mature aging and
155:
678:
regulation. Mutations are replicated when the cell replicates. In a population of cells, mutant cells will increase or decrease in frequency according to the effects of the mutation on the ability of the cell to survive and reproduce.
973:
HR requires the presence of an identical or nearly identical sequence to be used as a template for repair of the break. The enzymatic machinery responsible for this repair process is nearly identical to the machinery responsible for
1556:
it is known that LexA regulates transcription of approximately 48 genes including the lexA and recA genes. The SOS response is known to be widespread in the
Bacteria domain, but it is mostly absent in some bacterial phyla, like the
1733:
A number of individual genes have been identified as influencing variations in life span within a population of organisms. The effects of these genes is strongly dependent on the environment, in particular, on the organism's diet.
1467:(PCNA)-like group, two serine/threonine(S/T) kinases and their adaptors. Central to all DNA damage induced checkpoints responses is a pair of large protein kinases belonging to the first group of PI3K-like protein kinases-the ATM (
778:
and confers a level of resistance to alkylating agents upon sustained exposure by upregulation of alkylation repair enzymes. The third type of DNA damage reversed by cells is certain methylation of the bases cytosine and adenine.
2590:
describe the epigenetic alteration(s) and the cancer(s) in which these epimutations are found. Review articles, and broad experimental survey articles also document most of these epigenetic DNA repair deficiencies in cancers.
1669:
Experimental animals with genetic deficiencies in DNA repair often show decreased life span and increased cancer incidence. For example, mice deficient in the dominant NHEJ pathway and in telomere maintenance mechanisms get
2593:
Red-highlighted genes are frequently reduced or silenced by epigenetic mechanisms in various cancers. When these genes have low or absent expression, DNA damages can accumulate. Replication errors past these damages (see
3012:
to catalyze relevant chemical reactions has played a significant role in the elaboration of repair mechanisms during evolution. For an extremely detailed review of hypotheses relating to the evolution of DNA repair, see.
4807:"Mutational specificity of gamma-radiation-induced guanine-thymine and thymine-guanine intrastrand cross-links in mammalian cells and translesion synthesis past the guanine-thymine lesion by human DNA polymerase eta"
152:
1963:
is characterized by: increased replication initiation/origin firing; increased transcription and collisions of transcription-replication complexes; nucleotide deficiency; increase in reactive oxygen species (ROS).
681:
Although distinctly different from each other, DNA damage and mutation are related because DNA damage often causes errors of DNA synthesis during replication or repair; these errors are a major source of mutation.
761:
to repair damage from UV irradiation. Another type of damage, methylation of guanine bases, is directly reversed by the enzyme methyl guanine methyl transferase (MGMT), the bacterial equivalent of which is called
5906:
Dollé ME, Busuttil RA, Garcia AM, Wijnhoven S, van Drunen E, Niedernhofer LJ, et al. (April 2006). "Increased genomic instability is not a prerequisite for shortened lifespan in DNA repair deficient mice".
4727:
Stenerlöw B, Karlsson KH, Cooper B, Rydberg B. "Measurement of prompt DNA double-strand breaks in mammalian cells without including heat-labile sites: results for cells deficient in nonhomologous end joining".
1914:, two important genes whose mutations confer a hugely increased risk of breast cancer on carriers, are both associated with a large number of DNA repair pathways, especially NHEJ and homologous recombination.
1471:) and ATR (Ataxia- and Rad-related) kinases, whose sequence and functions have been well conserved in evolution. All DNA damage response requires either ATM or ATR because they have the ability to bind to the
2964:
In mice with a CRISPR-mediated homology-directed recombination insertion in their genome there were a large number of increased methylations of CpG sites within the double-strand break-associated insertion.
221:
of the double helix; that is, the bases themselves are chemically modified. These modifications can in turn disrupt the molecules' regular helical structure by introducing non-native chemical bonds or bulky
6186:
Cabelof DC, Yanamadala S, Raffoul JJ, Guo Z, Soofi A, Heydari AR (March 2003). "Caloric restriction promotes genomic stability by induction of base excision repair and reversal of its age-related decline".
1113:
during translesion synthesis may be preferable to resorting to more drastic mechanisms of DNA repair, which may cause gross chromosomal aberrations or cell death. In short, the process involves specialized
1279:
chromatin with phosphorylated γH2AX is about two million base pairs at the site of a DNA double-strand break. γH2AX does not, itself, cause chromatin decondensation, but within 30 seconds of irradiation,
841:, and the removed DNA region is then resynthesized. NER is a highly evolutionarily conserved repair mechanism and is used in nearly all eukaryotic and prokaryotic cells. In prokaryotes, NER is mediated by
7795:
Lee KH, Lee JS, Nam JH, Choi C, Lee MC, Park CS, et al. (October 2011). "Promoter methylation status of hMLH1, hMSH2, and MGMT genes in colorectal cancer associated with adenoma-carcinoma sequence".
837:
caused by UV light is usually repaired by a three-step process. First the damage is recognized, then 12-24 nucleotide-long strands of DNA are removed both upstream and downstream of the damage site by
6664:
Bartkova J, Rezaei N, Liontos M, Karakaidos P, Kletsas D, Issaeva N, et al. (November 2006). "Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints".
1247:
facilitates the mobilization of SIRT6 to DNA damage sites, and is required for efficient recruitment of poly (ADP-ribose) polymerase 1 (PARP1) to DNA break sites and for efficient repair of DSBs.
2956:
of the double-strand break, the involvement of DNMT1 causes the two repaired strands of DNA to have different levels of methylated cytosines. One strand becomes frequently methylated at about 21
811:(BER): damaged single bases or nucleotides are most commonly repaired by removing the base or the nucleotide involved and then inserting the correct base or nucleotide. In base excision repair, a
5965:
Kobayashi Y, Narumi I, Satoh K, Funayama T, Kikuchi M, Kitayama S, et al. (November 2004). "Radiation response mechanisms of the extremely radioresistant bacterium
Deinococcus radiodurans".
1313:. This larger complex rapidly associates with UV-induced damage within chromatin, with half-maximum association completed in 40 seconds. The PARP1 protein, attached to both DDB1 and DDB2, then
855:. These systems consist of at least two proteins. One detects the mismatch, and the other recruits an endonuclease that cleaves the newly synthesized DNA strand close to the region of damage. In
2518:
Deficient expression of DNA repair proteins due to an inherited mutation can cause increased risk of cancer. Individuals with an inherited impairment in any of 34 DNA repair genes (see article
1937:, which was approved by the Food and Drug Administration in 2015 for the treatment in women of BRCA-defective ovarian cancer. Tumor cells with partial loss of DNA damage response (specifically,
2746:). The selective advantage of DNA repair is to allow the cell to survive in the face of DNA damage. The selective advantage of epigenetic alterations that occur with DNA repair is not clear.
1605:
control, protein trafficking and degradation. Such genome wide transcriptional response is very complex and tightly regulated, thus allowing coordinated global response to damage. Exposure of
2563:
was repressed due to promoter methylation (PMS2 protein is unstable in the absence of MLH1). In the other 10 cases, loss of PMS2 expression was likely due to epigenetic overexpression of the
9989:
2463:
Epigenetic alterations refer to functionally relevant modifications to the genome that do not involve a change in the nucleotide sequence. Examples of such modifications are changes in
1895:
2633:, such cancers ordinarily have epigenetic deficiencies in other DNA repair genes. These repair deficiencies would likely cause increased unrepaired DNA damages. The over-expression of
8277:
Lam JS, Seligson DB, Yu H, Li A, Eeva M, Pantuck AJ, et al. (August 2006). "Flap endonuclease 1 is overexpressed in prostate cancer and is associated with a high
Gleason score".
6471:
Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, et al. (April 2005). "Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase".
815:
enzyme removes the damaged base from the DNA by cleaving the bond between the base and the deoxyribose. These enzymes remove a single base to create an apurinic or apyrimidinic site (
2918:
localizing to oxidized guanines. Polymerase beta is the main human polymerase in short-patch BER of oxidative DNA damage. Jiang et al. also found that polymerase beta recruited the
8595:"Promoter hypomethylation, especially around the E26 transformation-specific motif, and increased expression of poly (ADP-ribose) polymerase 1 in BRCA-mutated serous ovarian cancer"
6135:
Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B, et al. (July 2004). "Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase".
2838:
for six hours, 8-OHdG increased about 3.5-fold in DNA and this caused about 80% demethylation of the 5-methylcytosines in the genome. Demethylation of CpGs in a gene promoter by
9987:
5466:
Jazayeri A, Falck J, Lukas C, Bartek J, Smith GC, Lukas J, et al. (January 2006). "ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks".
139:
The DNA repair ability of a cell is vital to the integrity of its genome and thus to the normal functionality of that organism. Many genes that were initially shown to influence
42:
151:
1726:
1675:
DNA repair deficiency creates exactly the predicted effects; mice deficient in the NER pathway exhibited shortened life span without correspondingly higher rates of mutation.
9438:"Oxidative DNA Damage Modulates DNA Methylation Pattern in Human Breast Cancer 1 (BRCA1) Gene via the Crosstalk between DNA Polymerase β and a de novo DNA Methyltransferase"
548:
and tautomeric shift. Constitutive (spontaneous) DNA damage caused by endogenous oxidants can be detected as a low level of histone H2AX phosphorylation in untreated cells.
6610:
Bartkova J, Horejsí Z, Koed K, Krämer A, Tort F, Zieger K, et al. (April 2005). "DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis".
2574:
In a further example, epigenetic defects were found in various cancers (e.g. breast, ovarian, colorectal and head and neck). Two or three deficiencies in the expression of
544:
UV damage, alkylation/methylation, X-ray damage and oxidative damage are examples of induced damage. Spontaneous damage can include the loss of a base, deamination, sugar
4020:
Acharya PV (1971). "The isolation and partial characterization of age-correlated oligo-deoxyribo-ribonucleotides with covalently linked aspartyl-glutamyl polypeptides".
1374:
are activated. Checkpoint activation pauses the cell cycle and gives the cell time to repair the damage before continuing to divide. DNA damage checkpoints occur at the
660:), which is potentially lethal to an organism. Therefore, the induction of senescence and apoptosis is considered to be part of a strategy of protection against cancer.
2681:
joined, and then ligates the strands to create an intact DNA double helix. MMEJ almost always involves at least a small deletion, so that it is a mutagenic pathway.
92:. As a consequence, the DNA repair process is constantly active as it responds to damage in the DNA structure. When normal repair processes fail, and when cellular
9602:"Rapid and transient recruitment of DNMT1 to DNA double-strand breaks is mediated by its interaction with multiple components of the DNA damage response machinery"
7841:"Promoter CpG island hypermethylation of the DNA repair enzyme MGMT predicts clinical response to dacarbazine in a phase II study for metastatic colorectal cancer"
1787:, which suggests that genes conferring a large survival advantage early in life will be selected for even if they carry a corresponding disadvantage late in life.
4677:
Zahradka K, Slade D, Bailone A, Sommer S, Averbeck D, Petranovic M, et al. (October 2006). "Reassembly of shattered chromosomes in
Deinococcus radiodurans".
1475:
at the site of DNA damage, together with accessory proteins that are platforms on which DNA damage response components and DNA repair complexes can be assembled.
1251:
protein starts to appear at DNA damage sites in less than a second, with half maximum accumulation within 1.6 seconds after the damage occurs. PARP1 synthesizes
674:
damage, transcription of a gene can be prevented, and thus translation into a protein will also be blocked. Replication may also be blocked or the cell may die.
9988:
3057:
On some occasions, DNA damage is not repaired or is repaired by an error-prone mechanism that results in a change from the original sequence. When this occurs,
1871:") because those affected appear elderly and experience aging-related diseases at an abnormally young age, while not manifesting all the symptoms of old age.
970:
to the site for ligating the DNA ends, leading to an intact DNA. MMEJ is always accompanied by a deletion, so that MMEJ is a mutagenic pathway for DNA repair.
4520:"Microhomology-mediated End Joining and Homologous Recombination share the initial end resection step to repair DNA double-strand breaks in mammalian cells"
1894:
Because of inherent limitations in the DNA repair mechanisms, if humans lived long enough, they would all eventually develop cancer. There are at least 34
899:
DNA ligase, shown above repairing chromosomal damage, is an enzyme that joins broken nucleotides together by catalyzing the formation of an internucleotide
3008:); however, more complex organisms with more complex genomes have correspondingly more complex repair mechanisms. The ability of a large number of protein
2827:
to the 8-OHdG lesion (see Figure). This allows TET1 to demethylate an adjacent methylated cytosine. Demethylation of cytosine is an epigenetic alteration.
7656:"O(6)-methylguanine methyltransferase in colorectal cancers: detection of mutations, loss of expression, and weak association with G:C>A:T transitions"
986:
as a template. DSBs caused by the replication machinery attempting to synthesize across a single-strand break or unrepaired lesion cause collapse of the
1216:
presents a barrier to all DNA-based processes that require recruitment of enzymes to their sites of action. To allow DNA repair, the chromatin must be
4856:"Genetic requirement for mutagenesis of the G[8,5-Me]T cross-link in Escherichia coli: DNA polymerases IV and V compete for error-prone bypass"
2625:
repair. They are sometimes epigenetically over-expressed and sometimes under-expressed in certain cancers. As indicated in the
Knowledge articles on
2922:
protein DNMT3b to BER repair sites. They then evaluated the methylation pattern at the single nucleotide level in a small region of DNA including the
10093:
9005:"Mapping structurally defined guanine oxidation products along DNA duplexes: influence of local sequence context and endogenous cytosine methylation"
6359:
long enough, it is inevitable that at least one of his or her cells would eventually accumulate a set of mutations sufficient for cancer to develop.
2559:
expression, PMS2 was deficient in 6 due to mutations in the PMS2 gene, while in 103 cases PMS2 expression was deficient because its pairing partner
592:, exists in multiple copies, and is also tightly associated with a number of proteins to form a complex known as the nucleoid. Inside mitochondria,
8322:"Identification of gastric cancer-related genes using a cDNA microarray containing novel expressed sequence tags expressed in gastric cancer cells"
804:
mechanisms that remove the damaged nucleotide and replace it with an undamaged nucleotide complementary to that found in the undamaged DNA strand.
4238:"Saccharomyces cerevisiae Ku70 potentiates illegitimate DNA double-strand break repair and serves as a barrier to error-prone DNA repair pathways"
1642:
present during global response to DNA damage and are responsible for enhanced mutagenesis during a global response to DNA damage in eukaryotes.
2649:
over-expression and increased homologous recombinational repair to at least partially deal with such excess DNA damages. In those cases where
1941:
repair) are dependent on another mechanism – single-strand break repair – which is a mechanism consisting, in part, of the PARP1 gene product.
1493:
is induced by both p53-dependent and p53-independent mechanisms and can arrest the cell cycle at the G1/S and G2/M checkpoints by deactivating
1164:
or chemicals are prone to acquire multiple sites of bulky DNA lesions and double-strand breaks. Moreover, DNA damaging agents can damage other
9251:
Zhou X, Zhuang Z, Wang W, He L, Wu H, Cao Y, et al. (September 2016). "OGG1 is essential in oxidative stress induced DNA demethylation".
9057:
Zhou X, Zhuang Z, Wang W, He L, Wu H, Cao Y, et al. (September 2016). "OGG1 is essential in oxidative stress-induced DNA demethylation".
1283:
protein can be detected in association with γH2AX. RNF8 mediates extensive chromatin decondensation, through its subsequent interaction with
10043:
4189:"Cell cycle and genetic requirements of two pathways of nonhomologous end-joining repair of double-strand breaks in Saccharomyces cerevisiae"
1627:
cells. In an animal different types of cells are distributed among different organs that have evolved different sensitivities to DNA damage.
876:
Double-strand breaks, in which both strands in the double helix are severed, are particularly hazardous to the cell because they can lead to
4903:
10053:
7066:"Negative regulation of BRCA1 gene expression by HMGA1 proteins accounts for the reduced BRCA1 protein levels in sporadic breast carcinoma"
2733:, which can be recruited by the transcription machinery, lowering somatic mutation rates in active genes and other open chromatin regions.
3954:
Reardon JT, Sancar A (2006). "Purification and characterization of
Escherichia coli and human nucleotide excision repair enzyme systems".
3330:
2754:
In the steady state (with endogenous damages occurring and being repaired), there are about 2,400 oxidatively damaged guanines that form
2522:) have an increased risk of cancer, with some defects causing up to a 100% lifetime chance of cancer (e.g. p53 mutations). However, such
695:
420:, in which the wrong DNA base is stitched into place in a newly forming DNA strand, or a DNA base is skipped over or mistakenly inserted.
8189:"Epigenetic screen of human DNA repair genes identifies aberrant promoter methylation of NEIL1 in head and neck squamous cell carcinoma"
5992:
Spindler SR (September 2005). "Rapid and reversible induction of the longevity, anticancer and genomic effects of caloric restriction".
5135:"JNK Phosphorylates SIRT6 to Stimulate DNA Double-Strand Break Repair in Response to Oxidative Stress by Recruiting PARP1 to DNA Breaks"
9651:"DNA damage and Repair Modify DNA methylation and Chromatin Domain of the Targeted Locus: Mechanism of allele methylation polymorphism"
8956:"A reliable assessment of 8-oxo-2-deoxyguanosine levels in nuclear and mitochondrial DNA using the sodium iodide method to isolate DNA"
1430:
has also been identified. These proteins seem to be required for transmitting the checkpoint activation signal to downstream proteins.
5730:
Schlacher K, Pham P, Cox MM, Goodman MF (February 2006). "Roles of DNA polymerase V and RecA protein in SOS damage-induced mutation".
5509:
Bakkenist CJ, Kastan MB (January 2003). "DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation".
4287:"Efficient processing of DNA ends during yeast nonhomologous end joining. Evidence for a DNA polymerase beta (Pol4)-dependent pathway"
1601:
cells exposed to DNA damaging agents also activate important defensive pathways by inducing multiple proteins involved in DNA repair,
708:
as a template to recover the original information. Without access to a template, cells use an error-prone recovery mechanism known as
514:
residues per genome per generation) is too high in these species to be repaired by normal repair machinery, hence a possibility of an
3663:
2693:
hypomethylated, and this contributes to progression to endometrial cancer and BRCA-mutated serous ovarian cancer. Other genes in the
1899:
1235:
Chromatin relaxation occurs rapidly at the site of a DNA damage. In one of the earliest steps, the stress-activated protein kinase,
76:
per cell per day. Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to
10085:
4968:
Friedberg EC, Walker GC, Siede W, Wood RD, Schultz RA, Ellenberger T. (2006). DNA Repair and
Mutagenesis, part 3. ASM Press. 2nd ed.
1355:
are activated within 5 or 6 minutes after DNA is damaged. This is followed by phosphorylation of the cell cycle checkpoint protein
7462:"Double strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island"
3358:
10595:
2549:
10107:
7194:
1561:. The most common cellular signals activating the SOS response are regions of single-stranded DNA (ssDNA), arising from stalled
10569:
2682:
1976:), leading to increased tumor size and invasiveness. Humans born with inherited defects in DNA repair mechanisms (for example,
1403:
1352:
959:
536:
found in smoke, soot and tar create a huge diversity of DNA adducts- ethanoates, oxidized bases, alkylated phosphodiesters and
8363:"Flap endonuclease 1 is a promising candidate biomarker in gastric cancer and is involved in cell proliferation and apoptosis"
5375:"Dynamic in vivo interaction of DDB2 E3 ubiquitin ligase with UV-damaged DNA is independent of damage-recognition protein XPC"
8104:
6351:
5598:
5569:
4004:
3971:
3931:
3906:
3432:
3284:
Browner WS, Kahn AJ, Ziv E, Reiner AP, Oshima J, Cawthon RM, et al. (December 2004). "The genetics of human longevity".
3260:
3225:
1406:. ATM responds to DNA double-strand breaks and disruptions in chromatin structure, whereas ATR primarily responds to stalled
998:
system, MMEJ occurred in mammalian cells at the levels of 10–20% of HR when both HR and NHEJ mechanisms were also available.
10048:
2657:
are under-expressed, this would itself lead to increased unrepaired DNA damages. Replication errors past these damages (see
1829:
Mental retardation often accompanies the latter two disorders, suggesting increased vulnerability of developmental neurons.
1713:, the most radiation-resistant known organism, exhibit remarkable resistance to the double-strand break-inducing effects of
958:(PARP1) is required and may be an early step in MMEJ. There is pairing of microhomology regions followed by recruitment of
10230:
10102:
17:
7318:"Differing patterns of genetic instability in mice deficient in the mismatch repair genes Pms2, Mlh1, Msh2, Msh3 and Msh6"
6522:
Goldstein M, Kastan MB (2015). "The DNA damage response: implications for tumor responses to radiation and chemotherapy".
2769:
and where the cytosine is methylated (5-mCpG)). A 5-mCpG site has the lowest ionization potential for guanine oxidation.
924:. Besides its role as a genome caretaker, NHEJ is required for joining hairpin-capped double-strand breaks induced during
10285:
1019:
10538:
10469:
9884:"Sudden origins: a general mechanism of evolution based on stress protein concentration and rapid environmental change"
6084:
Tissenbaum HA, Guarente L (March 2001). "Increased dosage of a sir-2 gene extends lifespan in
Caenorhabditis elegans".
2766:
2698:
2694:
2673:
2539:
shows genes in the error-prone microhomology-mediated end joining pathway with increased expression in various cancers.
1464:
1452:
is damaged. It leads to a pause in cell cycle allowing the cell time to repair the damage before continuing to divide.
1321:. Action of ALC1 relaxes the chromatin at the site of UV damage to DNA. This relaxation allows other proteins in the
1129:
885:
8544:"Hypomethylation of ETS transcription factor binding sites and upregulation of PARP1 expression in endometrial cancer"
6972:, Ohm JE (February 2006). "Epigenetic gene silencing in cancer – a mechanism for early oncogenic pathway addiction?".
3045:, necessitated the evolution of DNA repair mechanisms that act specifically to counter the types of damage induced by
1487:
6766:
Halazonetis TD, Gorgoulis VG, Bartek J (March 2008). "An oncogene-induced DNA damage model for cancer development".
10553:
3127:
2805:
2743:
1614:
to DNA damaging agents results in overlapping but distinct transcriptional profiles. Similarities to environmental
188:
3491:"Constitutive histone H2AX phosphorylation and ATM activation, the reporters of DNA damage by endogenous oxidants"
1035:
9938:
1244:
533:
4737:
2804:
targets 8-OHdG and binds to the lesion without immediate excision. OGG1, present at a 5mCp-8-OHdG site recruits
4448:
4440:
3147:
2519:
1796:
3614:
Campisi J, d'Adda di Fagagna F (September 2007). "Cellular senescence: when bad things happen to good cells".
608:, create a highly oxidative environment that is known to damage mtDNA. A critical enzyme in counteracting the
8706:"Transcription restores DNA repair to heterochromatin, determining regional mutation rates in cancer genomes"
8403:
3729:
Sancar A (June 2003). "Structure and function of DNA photolyase and cryptochrome blue-light photoreceptors".
1468:
1456:
1399:
1348:
1274:
is also involved in the early steps leading to chromatin decondensation after DNA double-strand breaks. The
1145:
1014:
and other sources. At least two copies of the genome, with random DNA breaks, can form DNA fragments through
700:
Cells cannot function if DNA damage corrupts the integrity and accessibility of essential information in the
9759:"Non-homologous end joining induced alterations in DNA methylation: A source of permanent epigenetic change"
9337:"Targeted DNA demethylation and activation of endogenous genes using programmable TALE-TET1 fusion proteins"
5083:"The poly(ADP-ribose)-dependent chromatin remodeler Alc1 induces local chromatin relaxation upon DNA damage"
10528:
10435:
6422:
Gavande NS, VanderVere-Carozza PS, Hinshaw HD, Jalal SI, Sears CR, Pawelczak KS, et al. (April 2016).
3157:
1255:
729:
upon irradiation with UV light results in an abnormal covalent bond between adjacent pyrimidine bases. The
502:
bases from the DNA backbone) and single-strand breaks. For example, hydrolytic depurination is seen in the
330:
10090:
9143:"Lost in the Crowd: How Does Human 8-Oxoguanine DNA Glycosylase 1 (OGG1) Find 8-Oxoguanine in the Genome?"
8904:"Endogenous versus exogenous DNA adducts: their role in carcinogenesis, epidemiology, and risk assessment"
2491:, last for multiple cell generations, and can be considered to be epimutations (equivalent to mutations).
2483:. Each of these epigenetic alterations serves to regulate gene expression without altering the underlying
766:. This is an expensive process because each MGMT molecule can be used only once; that is, the reaction is
10718:
10713:
10037:
8187:
Chaisaingmongkol J, Popanda O, Warta R, Dyckhoff G, Herpel E, Geiselhart L, et al. (December 2012).
6271:
Walker DW, McColl G, Jenkins NL, Harris J, Lithgow GJ (May 2000). "Evolution of lifespan in C. elegans".
5615:
4043:
Bjorksten J, Acharya PV, Ashman S, Wetlaufer DB (July 1971). "Gerogenic fractions in the tritiated rat".
3198:
1973:
1695:
up-regulated compared to mouse. These observations suggest that elevated DNA repair facilitates greater
1437:
1314:
7367:"Disruption of Brca2 increases the spontaneous mutation rate in vivo: synergism with ionizing radiation"
7259:"Elevated levels of mutation in multiple tissues of mice deficient in the DNA mismatch repair gene Pms2"
2598:) can lead to increased mutations and, ultimately, cancer. Epigenetic repression of DNA repair genes in
2555:
Similarly, out of 119 cases of mismatch repair-deficient colorectal cancers that lacked DNA repair gene
10678:
10457:
10281:
10274:
9847:
O'Brien PJ (February 2006). "Catalytic promiscuity and the divergent evolution of DNA repair enzymes".
9708:"Detection of CRISPR-mediated genome modifications through altered methylation patterns of CpG islands"
3132:
2973:
2793:
2755:
2730:
1929:
Perhaps the most well-known of these 'synthetic lethality' drugs is the poly(ADP-ribose) polymerase 1 (
1651:
1322:
1026:
that can continue extension until complementary partner strands are found. In the final step, there is
881:
830:
758:
192:
7839:
Amatu A, Sartore-Bianchi A, Moutinho C, Belotti A, Bencardino K, Chirico G, et al. (April 2013).
10023:
7064:
Baldassarre G, Battista S, Belletti B, Thakur S, Pentimalli F, Trapasso F, et al. (April 2003).
5321:
Luijsterburg MS, Acs K, Ackermann L, Wiegant WW, Bekker-Jensen S, Larsen DH, et al. (May 2012).
3112:
3042:
2534:
1868:
1229:
954:
nuclease on either side of a double-strand break to reveal microhomology regions. In further steps,
877:
605:
9962:
8804:"Clustered Mutation Signatures Reveal that Error-Prone DNA Repair Targets Mutations to Active Genes"
8454:"Exploration of global gene expression patterns in pancreatic adenocarcinoma using cDNA microarrays"
8074:
7744:
Psofaki V, Kalogera C, Tzambouras N, Stephanou D, Tsianos E, Seferiadis K, et al. (July 2010).
6920:"CHK2 kinase expression is down-regulated due to promoter methylation in non-small cell lung cancer"
6224:"Mitochondrial and nuclear DNA base excision repair are affected differently by caloric restriction"
5373:
Luijsterburg MS, Goedhart J, Moser J, Kool H, Geverts B, Houtsmuller AB, et al. (August 2007).
5272:
Mailand N, Bekker-Jensen S, Faustrup H, Melander F, Bartek J, Lukas C, et al. (November 2007).
3450:"UV Sensitivity and Mutagenesis of the Extremely Thermophilic Eubacterium Thermus thermophilus HB27"
3298:
1418:
cascade, eventually leading to cell cycle arrest. A class of checkpoint mediator proteins including
10452:
10374:
10223:
9335:
Maeder ML, Angstman JF, Richardson ME, Linder SJ, Cascio VM, Tsai SQ, et al. (December 2013).
3683:
2953:
2622:
2508:
1938:
1813:: hypersensitivity to sunlight/UV, resulting in increased skin cancer incidence and premature aging
1610:
1540:
1236:
889:
738:
206:) can impede a cell's ability to carry out its function and appreciably increase the likelihood of
164:
96:
does not occur, irreparable DNA damage may occur. This can eventually lead to malignant tumors, or
9922:
8755:"The histone mark H3K36me3 regulates human DNA mismatch repair through its interaction with MutSα"
8452:
Iacobuzio-Donahue CA, Maitra A, Olsen M, Lowe AW, van Heek NT, Rosty C, et al. (April 2003).
5323:"A new non-catalytic role for ubiquitin ligase RNF8 in unfolding higher-order chromatin structure"
5274:"RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins"
2792:-pG, or 5mCpG. Reactive oxygen species (ROS) may attack guanine at the dinucleotide site, forming
2526:(which cause highly penetrant cancer syndromes) are the cause of only about 1 percent of cancers.
795:
excising a hydrolytically-produced uracil residue from DNA. The uracil residue is shown in yellow.
10060:
9706:
Farris MH, Texter PA, Mora AA, Wiles MV, Mac Garrigle EF, Klaus SA, et al. (December 2020).
8853:
Polak P, Lawrence MS, Haugen E, Stoletzki N, Stojanov P, Thurman RE, et al. (January 2014).
5417:
Pines A, Vrouwe MG, Marteijn JA, Typas D, Luijsterburg MS, Cansoy M, et al. (October 2012).
5187:"PARP1-dependent kinetics of recruitment of MRE11 and NBS1 proteins to multiple DNA damage sites"
4907:
3331:"Nobel Prize in Chemistry Awarded to Tomas Lindahl, Paul Modrich and Aziz Sancar for DNA Studies"
2985:
2863:
was reduced (an epigenetic alteration) and this allowed about 6.5 fold increase of expression of
1709:
1498:
1098:
1006:
670:
593:
262:
77:
9952:
8503:"Increased expression and no mutation of the Flap endonuclease (FEN1) gene in human lung cancer"
6561:
6037:"Potential anti-aging agents suppress the level of constitutive mTOR- and DNA damage- signaling"
2772:
10564:
10474:
10269:
9808:"Recombination at double-strand breaks and DNA ends: conserved mechanisms from phage to humans"
7611:
Fearon ER (November 1997). "Human cancer syndromes: clues to the origin and nature of cancer".
5133:
Van Meter M, Simon M, Tombline G, May A, Morello TD, Hubbard BP, et al. (September 2016).
3678:
3293:
2813:
2801:
2784:. In adult somatic cells DNA methylation typically occurs in the context of CpG dinucleotides (
1767:
1631:
1630:
In general global response to DNA damage involves expression of multiple genes responsible for
1221:
1132:(PCNA). Under normal circumstances, PCNA bound to polymerases replicates the DNA. At a site of
852:
792:
601:
7703:
Shen L, Kondo Y, Rosner GL, Xiao L, Hernandez NS, Vilaythong J, et al. (September 2005).
5849:
de Boer J, Andressoo JO, de Wit J, Huijmans J, Beems RB, van Steeg H, et al. (May 2002).
5419:"PARP1 promotes nucleotide excision repair through DDB2 stabilization and recruitment of ALC1"
5185:
Haince JF, McDonald D, Rodrigue A, Déry U, Masson JY, Hendzel MJ, et al. (January 2008).
2511:
repair (HRR). Chromosomal rearrangements and aneuploidy also increase in HRR defective cells.
2471:, changes in chromosomal architecture (caused by inappropriate expression of proteins such as
1898:. Many of these mutations cause DNA repair to be less effective than normal. In particular,
640:
that cap chromosomes and undergo partial degradation each time a cell undergoes division (see
10330:
8501:
Sato M, Girard L, Sekine I, Sunaga N, Ramirez RD, Kamibayashi C, et al. (October 2003).
8402:
Krause A, Combaret V, Iacono I, Lacroix B, Compagnon C, Bergeron C, et al. (July 2005).
7416:"Bloom's syndrome. I. Genetical and clinical observations in the first twenty-seven patients"
4417:
2949:
2919:
2582:
or PMS2 occur simultaneously in the majority of 49 colon cancers evaluated by Facista et al.
1856:
1810:
1635:
1602:
1371:
1340:
1044:
introduce both single- and double-strand breaks in the course of changing the DNA's state of
1027:
983:
975:
503:
266:
203:
123:
8855:"Reduced local mutation density in regulatory DNA of cancer genomes is linked to DNA repair"
8646:"Differential DNA mismatch repair underlies mutation rate variation across the human genome"
8230:"Overexpression and hypomethylation of flap endonuclease 1 gene in breast and other cancers"
8138:
Krishnan K, Steptoe AL, Martin HC, Wani S, Nones K, Waddell N, et al. (February 2013).
6373:"The BRCA1/2 pathway prevents hematologic cancers in addition to breast and ovarian cancers"
5081:
Sellou H, Lebeaupin T, Chapuis C, Smith R, Hegele A, Singh HR, et al. (December 2016).
3020:
indicates that single-cell life began to proliferate on the planet at some point during the
845:. In eukaryotes, many more proteins are involved, although the general strategy is the same.
584:. In either state the DNA is highly compacted and wound up around bead-like proteins called
265:
produced from normal metabolic byproducts (spontaneous mutation), especially the process of
10255:
10169:
10019:
9662:
9549:
Cuozzo C, Porcellini A, Angrisano T, Morano A, Lee B, Di Pardo A, et al. (July 2007).
9500:
9386:"Mismatch repair proteins recruit DNA methyltransferase 1 to sites of oxidative DNA damage"
9205:
8657:
7978:
7965:
Valeri N, Gasparini P, Fabbri M, Braconi C, Veronese A, Lovat F, et al. (April 2010).
7620:
7511:
Cuozzo C, Porcellini A, Angrisano T, Morano A, Lee B, Di Pardo A, et al. (July 2007).
7270:
6874:
6775:
6673:
6619:
6480:
6144:
6093:
5916:
5862:
5778:
5518:
4758:"Eukaryotic translesion polymerases and their roles and regulation in DNA damage tolerance"
4686:
4531:
4143:
3850:
3461:
2911:
2797:
2715:
2468:
1977:
1902:(HNPCC) is strongly associated with specific mutations in the DNA mismatch repair pathway.
1836:
1569:
to separate the two DNA strands. In the initiation step, RecA protein binds to ssDNA in an
1333:
1225:
1217:
1184:. The accumulation of damage, to be specific, double-strand breaks or adducts stalling the
808:
613:
211:
33:
9649:
Russo G, Landi R, Pezone A, Morano A, Zuchegna C, Romano A, et al. (September 2016).
8026:"Deficient expression of DNA repair enzymes in early progression to sporadic colon cancer"
7926:"Immunohistochemical analysis reveals high frequency of PMS2 defects in colorectal cancer"
7924:
Truninger K, Menigatti M, Luz J, Russell A, Haider R, Gebbers JO, et al. (May 2005).
6315:
3766:"Evolution of mutation rates: phylogenomic analysis of the photolyase/cryptochrome family"
3704:
3082:
A technology named clustered regularly interspaced short palindromic repeat (shortened to
3069:, the mutation has the potential to be passed on to the organism's offspring. The rate of
2968:
8:
10728:
10708:
10665:
10352:
10216:
10004:
9192:
Lan L, Nakajima S, Oohata Y, Takao M, Okano S, Masutani M, et al. (September 2004).
8954:
Hamilton ML, Guo Z, Fuller CD, Van Remmen H, Ward WF, Austad SN, et al. (May 2001).
6818:
5802:"Shorter telomeres, accelerated ageing and increased lymphoma in DNA-PKcs-deficient mice"
3162:
2936:
2923:
2842:
activity increases transcription of the gene into messenger RNA. In cells treated with H
2722:
2504:
1822:
1784:
1735:
1415:
1343:
are activated to allow DNA repair to occur before the cell cycle progresses. First, two
1106:
1015:
925:
851:
systems are present in essentially all cells to correct errors that are not corrected by
842:
597:
537:
470:
345:
113:
88:
in the cell's genome, which affect the survival of its daughter cells after it undergoes
10173:
9666:
9504:
9209:
8704:
Zheng CL, Wang NJ, Chung J, Moslehi H, Sanborn JZ, Hur JS, et al. (November 2014).
8661:
8024:
Facista A, Nguyen H, Lewis C, Prasad AR, Ramsey L, Zaitlin B, et al. (April 2012).
7982:
7624:
7274:
6878:
6779:
6677:
6623:
6484:
6148:
6097:
5920:
5866:
5522:
5029:"Cytometric detection of chromatin relaxation, an early reporter of DNA damage response"
4690:
4579:"Homology and enzymatic requirements of microhomology-dependent alternative end joining"
4535:
4147:
3854:
3465:
3359:"The Nobel Prize in Chemistry 2015 – DNA repair – providing chemical stability for life"
1968:
models, loss of DNA damage response-mediated cell senescence was observed after using a
1097:
introduces mutations at these sites. Pol η is known to add the first adenine across the
10192:
10157:
10139:
10114:
9783:
9758:
9734:
9707:
9683:
9650:
9626:
9601:
9577:
9550:
9523:
9488:
9464:
9437:
9410:
9385:
9361:
9336:
9312:
9287:
9169:
9142:
9118:
9093:
9029:
9004:
8928:
8903:
8879:
8854:
8779:
8754:
8730:
8705:
8678:
8645:
8621:
8594:
8570:
8543:
8478:
8453:
8434:
8302:
8254:
8229:
8164:
8139:
8115:
8052:
8025:
8001:
7966:
7906:
7821:
7772:
7745:
7680:
7655:
7588:
7563:
7539:
7512:
7488:
7461:
7432:
7415:
7391:
7366:
7342:
7317:
7234:
7207:
7180:
7155:
7041:
7016:
6997:
6895:
6862:
6799:
6748:
6697:
6643:
6592:
6504:
6448:
6423:
6399:
6372:
6320:
6296:
6253:
6168:
6117:
6061:
6036:
6017:
5888:
5826:
5801:
5587:
5542:
5491:
5443:
5418:
5347:
5322:
5303:
5159:
5134:
5107:
5082:
5053:
5028:
5004:
4979:
4880:
4855:
4831:
4806:
4782:
4757:
4756:
Waters LS, Minesinger BK, Wiltrout ME, D'Souza S, Woodruff RV, Walker GC (March 2009).
4710:
4654:
4627:
4603:
4578:
4554:
4519:
4497:
4253:
4169:
4068:
4056:
3874:
3790:
3765:
3639:
3515:
3490:
3335:
3030:
2907:
2690:
2496:
1960:
1806:
Defects in the NER mechanism are responsible for several genetic disorders, including:
1751:
1547:
1157:
1086:
1011:
978:
during meiosis. This pathway allows a damaged chromosome to be repaired using a sister
653:
477:
246:(in eukaryotes), and both superstructures are vulnerable to the effects of DNA damage.
235:
101:
9824:
9807:
9436:
Jiang Z, Lai Y, Beaver JM, Tsegay PS, Zhao ML, Horton JK, et al. (January 2020).
9228:
9193:
8902:
Swenberg JA, Lu K, Moeller BC, Gao L, Upton PB, Nakamura J, et al. (March 2011).
8469:
8404:"Genome-wide analysis of gene expression in neuroblastomas detected by mass screening"
7090:
7065:
6946:
6919:
6535:
6200:
4942:
4484:
4467:
4401:
4376:
4352:
4327:
4262:
4237:
4213:
4188:
3963:
3061:
may propagate into the genomes of the cell's progeny. Should such an event occur in a
2808:
and TET1 oxidizes the 5mC adjacent to the 8-OHdG. This initiates demethylation of 5mC.
1573:
driven reaction creating RecA–ssDNA filaments. RecA–ssDNA filaments activate LexA auto
10723:
10548:
10197:
10156:
Morales ME, Derbes RS, Ade CM, Ortego JC, Stark J, Deininger PL, et al. (2016).
10144:
9905:
9864:
9829:
9788:
9739:
9688:
9631:
9582:
9528:
9469:
9415:
9366:
9317:
9268:
9233:
9174:
9123:
9074:
9034:
8985:
8980:
8955:
8933:
8884:
8835:
8784:
8735:
8683:
8626:
8575:
8524:
8483:
8426:
8384:
8343:
8294:
8290:
8259:
8210:
8169:
8120:
8100:
8087:
Jin B, Robertson KD (2013). "DNA Methyltransferases, DNA Damage Repair, and Cancer".
8057:
8006:
7947:
7898:
7862:
7813:
7777:
7726:
7685:
7636:
7593:
7544:
7493:
7437:
7396:
7347:
7298:
7293:
7258:
7239:
7185:
7136:
7095:
7046:
7032:
6989:
6969:
6951:
6900:
6843:
6791:
6740:
6689:
6635:
6584:
6539:
6496:
6453:
6439:
6404:
6347:
6288:
6245:
6204:
6160:
6109:
6066:
6009:
5974:
5932:
5880:
5831:
5782:
5765:
Fry RC, Begley TJ, Samson LD (2004). "Genome-wide responses to DNA-damaging agents".
5747:
5712:
5707:
5690:
5668:
5627:
5594:
5565:
5534:
5483:
5448:
5396:
5352:
5295:
5254:
5208:
5164:
5112:
5058:
5009:
4946:
4885:
4836:
4787:
4739:
4702:
4659:
4608:
4559:
4489:
4429:
4406:
4357:
4308:
4267:
4218:
4161:
4112:
4060:
4025:
4000:
3977:
3967:
3927:
3902:
3866:
3823:
3795:
3746:
3696:
3631:
3596:
3561:
3520:
3428:
3405:
3311:
3266:
3256:
3142:
2903:
2777:
2545:
2523:
1969:
1816:
1679:
1288:
1161:
947:
775:
730:
529:
515:
454:
386:
382:
218:
10077:
8438:
8306:
7910:
7081:
6803:
6752:
6596:
6257:
6172:
5892:
5307:
4577:
Sharma S, Javadekar SM, Pandey M, Srivastava M, Kumari R, Raghavan SC (March 2015).
4501:
4072:
3878:
3643:
3251:
Lodish H, Berk A, Matsudaira P, Kaiser CA, Krieger M, Scott MP, et al. (2004).
2935:
transcription start site, and negative numbers indicate nucleotides in the upstream
2886:
incubation appear to promote other epigenetic alterations. Treatment of cells with H
10187:
10177:
10134:
10126:
10072:
9895:
9856:
9819:
9778:
9770:
9729:
9719:
9678:
9670:
9621:
9613:
9572:
9562:
9518:
9508:
9459:
9449:
9405:
9397:
9356:
9348:
9307:
9299:
9260:
9223:
9213:
9164:
9154:
9113:
9105:
9066:
9024:
9016:
9003:
Ming X, Matter B, Song M, Veliath E, Shanley R, Jones R, et al. (March 2014).
8975:
8967:
8923:
8915:
8874:
8866:
8825:
8815:
8774:
8766:
8725:
8717:
8673:
8665:
8616:
8606:
8565:
8555:
8514:
8473:
8465:
8418:
8374:
8333:
8286:
8249:
8241:
8200:
8159:
8151:
8110:
8092:
8047:
8037:
7996:
7986:
7937:
7890:
7852:
7825:
7805:
7767:
7757:
7746:"Promoter methylation status of hMLH1, MGMT, and CDKN2A/p16 in colorectal adenomas"
7716:
7675:
7667:
7628:
7583:
7575:
7534:
7524:
7483:
7473:
7427:
7386:
7378:
7337:
7329:
7316:
Hegan DC, Narayanan L, Jirik FR, Edelmann W, Liskay RM, Glazer PM (December 2006).
7288:
7278:
7229:
7219:
7175:
7167:
7126:
7085:
7077:
7036:
7028:
7001:
6981:
6941:
6931:
6890:
6882:
6833:
6783:
6732:
6724:
6715:
Gaillard H, García-Muse T, Aguilera A (May 2015). "Replication stress and cancer".
6701:
6681:
6647:
6627:
6576:
6531:
6508:
6488:
6443:
6435:
6394:
6384:
6300:
6280:
6235:
6196:
6152:
6121:
6101:
6056:
6048:
6021:
6001:
5924:
5870:
5821:
5813:
5800:
Espejel S, Martín M, Klatt P, Martín-Caballero J, Flores JM, Blasco MA (May 2004).
5774:
5739:
5702:
5658:
5546:
5526:
5495:
5475:
5438:
5430:
5386:
5342:
5334:
5285:
5244:
5198:
5154:
5146:
5102:
5094:
5048:
5040:
4999:
4991:
4938:
4929:
Wang Z (July 2001). "Translesion synthesis by the UmuC family of DNA polymerases".
4875:
4867:
4826:
4818:
4777:
4769:
4733:
4714:
4694:
4649:
4639:
4598:
4590:
4549:
4539:
4479:
4421:
4396:
4388:
4347:
4339:
4298:
4257:
4249:
4208:
4200:
4173:
4151:
4102:
4052:
3959:
3858:
3785:
3777:
3738:
3688:
3623:
3588:
3551:
3510:
3502:
3469:
3401:
3397:
3303:
3046:
3009:
2851:
2789:
1739:
1562:
1552:
1519:
1407:
1326:
1317:(creates a poly-ADP ribose chain) on DDB2 that attracts the DNA remodeling protein
1302:
1185:
987:
834:
726:
648:
is a reversible state of cellular dormancy that is unrelated to genome damage (see
449:
238:
and therefore damage or disturbance does not occur at that level. DNA is, however,
73:
9264:
9194:"In situ analysis of repair processes for oxidative DNA damage in mammalian cells"
9070:
8245:
7857:
7840:
7632:
7382:
3556:
3539:
2676:(MMEJ) pathway and are up-regulated in cancer. MMEJ is an additional error-prone
1972:(shRNA) to inhibit the double-strand break response kinase ataxia telangiectasia (
369:
of bases and generation of DNA strand interruptions from reactive oxygen species,
10264:
10182:
10097:
9567:
8721:
8422:
7942:
7925:
7529:
7478:
5928:
5150:
3841:
Volkert MR (1988). "Adaptive response of Escherichia coli to alkylation damage".
3307:
3137:
3024:
period, although exactly when recognizably modern life first emerged is unclear.
2759:
2711:
2464:
1514:
1411:
1061:
933:
929:
848:
820:
812:
801:
417:
349:
140:
8096:
6035:
Halicka HD, Zhao H, Li J, Lee YS, Hsieh TC, Wu JM, et al. (December 2012).
3220:
2704:
1738:
reproducibly results in extended lifespan in a variety of organisms, likely via
10692:
9957:
9724:
9600:
Ha K, Lee GE, Palii SS, Brown KD, Takeda Y, Liu K, et al. (January 2011).
9109:
8820:
8803:
8770:
8338:
8321:
8091:. Advances in Experimental Medicine and Biology. Vol. 754. pp. 3–29.
7971:
Proceedings of the National Academy of Sciences of the United States of America
7263:
Proceedings of the National Academy of Sciences of the United States of America
6339:
5290:
5273:
4995:
4524:
Proceedings of the National Academy of Sciences of the United States of America
3167:
3103:
3034:
2915:
2860:
2603:
1946:
can repair the damage with the functioning homologous recombination mechanism.
1875:
1842:
1743:
1687:
1615:
1570:
1460:
1110:
1073:
767:
641:
525:
360:
There are several types of damage to DNA due to endogenous cellular processes:
53:
9774:
8320:
Kim JM, Sohn HY, Yoon SY, Oh JH, Yang JO, Kim JH, et al. (January 2005).
7894:
7809:
6838:
6005:
5691:"Aeons of distress: an evolutionary perspective on the bacterial SOS response"
5233:"DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139"
2943:
2749:
1060:
Translesion synthesis (TLS) is a DNA damage tolerance process that allows the
868:
10702:
10576:
10397:
9487:
Mortusewicz O, Schermelleh L, Walter J, Cardoso MC, Leonhardt H (June 2005).
8971:
7762:
7579:
5817:
4644:
4343:
4303:
4286:
3827:
3489:
Tanaka T, Halicka HD, Huang X, Traganos F, Darzynkiewicz Z (September 2006).
3017:
2997:
2932:
2899:
2488:
1879:
1714:
1620:
1201:
1065:
1041:
940:
637:
581:
365:
168:
9513:
9218:
8919:
8611:
7991:
7671:
7333:
7131:
7114:
6787:
6389:
6156:
5875:
5850:
5249:
5232:
5098:
4544:
3781:
3448:
Ohta T, Tokishita SI, Mochizuki K, Kawase J, Sakahira M, Yamagata H (2006).
3270:
1243:
on serine 10 in response to double-strand breaks or other DNA damage. This
1232:
are two predominant factors employed to accomplish this remodeling process.
632:, is a protective response to the shortening of the chromosome ends, called
10543:
10512:
10462:
10445:
10392:
10345:
10201:
10148:
9909:
9868:
9833:
9792:
9743:
9692:
9635:
9586:
9532:
9473:
9419:
9384:
Ding N, Bonham EM, Hannon BE, Amick TR, Baylin SB, O'Hagan HM (June 2016).
9370:
9321:
9272:
9237:
9178:
9127:
9078:
9038:
8989:
8937:
8888:
8839:
8788:
8739:
8687:
8630:
8579:
8528:
8519:
8502:
8487:
8430:
8388:
8379:
8362:
8347:
8298:
8263:
8228:
Singh P, Yang M, Dai H, Yu D, Huang Q, Tan W, et al. (November 2008).
8214:
8173:
8155:
8124:
8061:
8010:
7951:
7902:
7866:
7817:
7781:
7730:
7689:
7597:
7548:
7497:
7400:
7351:
7283:
7243:
7189:
7140:
7099:
7050:
6993:
6955:
6936:
6904:
6847:
6795:
6744:
6693:
6639:
6588:
6543:
6500:
6457:
6408:
6292:
6249:
6208:
6164:
6113:
6070:
6013:
5978:
5936:
5884:
5835:
5786:
5751:
5716:
5672:
5663:
5646:
5631:
5538:
5487:
5452:
5400:
5356:
5338:
5299:
5212:
5203:
5186:
5168:
5116:
5062:
5027:
Halicka HD, Zhao H, Podhorecka M, Traganos F, Darzynkiewicz Z (July 2009).
5013:
4950:
4889:
4840:
4791:
4743:
4706:
4663:
4612:
4563:
4493:
4433:
4410:
4361:
4312:
4116:
4107:
4090:
3981:
3799:
3750:
3700:
3635:
3600:
3592:
3565:
3524:
3409:
3315:
3152:
3038:
3025:
2484:
1922:
1918:
1883:
1566:
1510:
1258:(poly (ADP-ribose) or PAR) chains on itself. Next the chromatin remodeler
1173:
1078:
1002:
838:
774:. A generalized response to methylating agents in bacteria is known as the
565:
561:
560:
cells in general, DNA is found in two cellular locations – inside the
495:
466:
401:
172:
10130:
9401:
8560:
8042:
7721:
7705:"MGMT promoter methylation and field defect in sporadic colorectal cancer"
7704:
7640:
7441:
7302:
7224:
7171:
6240:
6052:
5434:
5258:
4773:
4594:
4425:
4375:
Wang H, Perrault AR, Takeda Y, Qin W, Wang H, Iliakis G (September 2003).
4271:
4222:
4204:
4165:
4064:
4029:
3870:
3862:
3692:
3579:
Lynch MD (February 2006). "How does cellular senescence prevent cancer?".
2661:) could cause increased mutations and cancer, so that under-expression of
1707:). On the other hand, organisms with enhanced DNA repair systems, such as
1394:
checkpoint also exists. Checkpoint activation is controlled by two master
787:
430:
Damage caused by exogenous agents comes in many forms. Some examples are:
10158:"Heavy Metal Exposure Influences Double Strand Break DNA Repair Outcomes"
9617:
9454:
9303:
9159:
9094:"The genomics of oxidative DNA damage, repair, and resulting mutagenesis"
8205:
8188:
7879:
5044:
4518:
Truong LN, Li Y, Shi LZ, Hwang PY, He J, Wang H, et al. (May 2013).
4392:
3506:
3474:
3449:
3366:
3177:
3021:
2989:
2839:
2824:
2457:
1762:
1586:
1558:
1524:
1165:
1115:
1090:
577:
545:
507:
483:
397:
378:
282:
176:
10007:
was created from a revision of this article dated 17 June 2005
8669:
7365:
Tutt AN, van Oostrom CT, Ross GM, van Steeg H, Ashworth A (March 2002).
6736:
6685:
6631:
6492:
6222:
Stuart JA, Karahalil B, Hogue BA, Souza-Pinto NC, Bohr VA (March 2004).
5530:
4698:
4089:
Liang L, Deng L, Chen Y, Li GC, Shao C, Tischfield JA (September 2005).
962:(FEN1) to remove overhanging flaps. This is followed by recruitment of
84:
that the affected DNA encodes. Other lesions induce potentially harmful
10479:
10300:
9900:
9883:
8830:
7257:
Narayanan L, Fritzell JA, Baker SM, Liskay RM, Glazer PM (April 1997).
6580:
5391:
5374:
4437:. If this is an intentional citation to a such a paper, please replace
3182:
3122:
2993:
2969:
Non-homologous end joining can cause some epigenetic marker alterations
2641:
seen in these cancers may reflect selective pressures for compensatory
1985:
1780:
1755:
1717:, likely due to enhanced efficiency of DNA repair and especially NHEJ.
1639:
1598:
1472:
1441:
1368:
1337:
1197:
937:
913:
823:
742:
734:
649:
589:
573:
557:
407:
392:
373:
306:
258:
198:
65:
9860:
9757:
Allen B, Pezone A, Porcellini A, Muller MT, Masternak MM (June 2017).
9674:
9020:
8753:
Li F, Mao G, Tong D, Huang J, Gu L, Yang W, et al. (April 2013).
6886:
6424:"DNA repair targeted therapy: The past or future of cancer treatment?"
5743:
4871:
4822:
4328:"Processing of DNA for nonhomologous end-joining by cell-free extract"
3742:
3540:"Oncogene-induced senescence: putting the brakes on tumor development"
3388:
Roulston A, Marcellus RC, Branton PE (1999). "Viruses and apoptosis".
2830:
As an example, when human mammary epithelial cells were treated with H
1765:
of the gene SIR-2, which regulates DNA packaging in the nematode worm
725:
not involve breakage of the phosphodiester backbone. The formation of
656:. Unregulated cell division can lead to the formation of a tumor (see
9352:
8870:
6421:
6284:
6105:
3117:
3070:
3062:
2878:
causes considerable demethylation of 5-mCpG sites, shorter times of H
2785:
1846:
1696:
1624:
1593:
1543:
1536:
1483:
1445:
1252:
1213:
1189:
1102:
1045:
979:
921:
771:
705:
633:
617:
569:
301:
290:
286:
272:
239:
119:
93:
69:
9140:
8186:
7115:"Mutator pathways unleashed by epigenetic silencing in human cancer"
6985:
6863:"DNA damage response genes and the development of cancer metastasis"
6728:
6223:
5616:"The role of the cyclin-dependent kinase inhibitor p21 in apoptosis"
5479:
5271:
3627:
903:
bond between the phosphate backbone and the deoxyribose nucleotides.
410:(e.g., benzopyrene diol epoxide-dG adduct, aristolactam I-dA adduct)
179:
for their work on the molecular mechanisms of DNA repair processes.
143:
have turned out to be involved in DNA damage repair and protection.
10687:
10560:
9486:
8140:"MicroRNA-182-5p targets a network of genes involved in DNA repair"
7838:
6562:"DNA repair, genome stability and cancer: a historical perspective"
5851:"Premature aging in mice deficient in DNA repair and transcription"
4755:
3172:
3097:
3058:
3005:
2957:
2820:
2781:
2762:
2726:
2718:
2564:
2480:
1942:
1934:
1896:
Inherited human DNA repair gene mutations that increase cancer risk
1874:
Other diseases associated with reduced DNA repair function include
1864:
1850:
1671:
1574:
1383:
1375:
1287:, a component of the nucleosome remodeling and deacetylase complex
1192:. The common features of global response are induction of multiple
1140:
1105:
and the second adenine will be added in its syn conformation using
746:
737:, whose activation is obligately dependent on energy absorbed from
645:
609:
585:
461:
440:
435:
423:
Monoadduct damage cause by change in single nitrogenous base of DNA
326:
85:
72:
can cause DNA damage, resulting in tens of thousands of individual
7743:
5799:
5231:
Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM (March 1998).
4156:
4131:
3822:(5th ed.). Pearson Benjamin Cummings; CSHL Press. Ch. 9, 10.
2529:
1359:, initiating its function, about 10 minutes after DNA is damaged.
733:
process directly reverses this damage by the action of the enzyme
10507:
10259:
9141:
D'Augustin O, Huet S, Campalans A, Radicella JP (November 2020).
7654:
Halford S, Rowan A, Sawyer E, Talbot I, Tomlinson I (June 2005).
7063:
6326:
If we lived long enough, sooner or later we all would get cancer.
4377:"Biochemical evidence for Ku-independent backup pathways of NHEJ"
3818:
Watson JD, Baker TA, Bell SP, Gann A, Levine M, Losick R (2004).
2568:
1585:, SOS boxes are 20-nucleotide long sequences near promoters with
1391:
1387:
1379:
1275:
1169:
1069:
1018:. Partially overlapping fragments are then used for synthesis of
816:
754:
629:
444:
322:
243:
227:
89:
9923:"CRISPR gene-editing tool has scientists thrilled – but nervous"
8451:
7967:"Modulation of mismatch repair and genomic stability by miR-155"
2819:
When OGG1 is present at an oxidized guanine within a methylated
2796:(8-OHdG), and resulting in a 5mCp-8-OHdG dinucleotide site. The
628:
Senescence, an irreversible process in which the cell no longer
128:
unregulated cell division, which can lead to the formation of a
10632:
10387:
10340:
10335:
10032:
9548:
8077:, 15 April 2014, MD Anderson Cancer Center, University of Texas
7510:
7205:
6663:
6221:
5320:
4576:
4468:"Unraveling V(D)J recombination; insights into gene regulation"
4042:
3083:
3066:
3049:. The mechanism by which this came about, however, is unclear.
1729:
Most life span influencing genes affect the rate of DNA damage.
1661:
1494:
1395:
1344:
1264:
1133:
1023:
763:
701:
657:
511:
499:
223:
133:
97:
61:
10061:"Human DNA repair diseases: From genome instability to cancer"
9334:
6918:
Zhang P, Wang J, Gao W, Yuan BZ, Rogers J, Reed E (May 2004).
5848:
4628:"Alternative end-joining mechanisms: a historical perspective"
2914:(BER) of oxidative damage occurred with the DNA repair enzyme
1665:
DNA repair rate is an important determinant of cell pathology.
41:
10647:
10642:
10637:
10627:
10620:
10615:
10610:
10605:
10600:
10590:
10585:
10440:
10404:
10325:
10320:
10315:
10305:
10208:
7206:
Bernstein C, Nfonsam V, Prasad AR, Bernstein H (March 2013).
5372:
5026:
4132:"Yeast DNA ligase IV mediates non-homologous DNA end joining"
3187:
3001:
2927:
2812:
Oxidized guanine has mispairing potential and is mutagenic.
2705:
Genome-wide distribution of DNA repair in human somatic cells
2630:
2626:
2617:
2611:
2579:
2575:
2476:
2472:
2339:
2182:
2151:
1930:
1910:
1904:
1691:
1683:
1606:
1427:
1419:
1356:
1318:
1310:
1306:
1271:
1259:
1248:
1240:
1177:
1137:
963:
955:
951:
917:
900:
895:
750:
745:) to promote catalysis. Photolyase, an old enzyme present in
696:
DNA damage (naturally occurring) § Repair of damaged DNA
335:
316:
313:
297:
207:
129:
9489:"Recruitment of DNA methyltransferase I to DNA repair sites"
8852:
7964:
7923:
7364:
7256:
5964:
5905:
5647:"Some aspects of the SOS response system--a critical survey"
3613:
3447:
2697:
pathway are also over-expressed in a number of cancers (see
1859:: sensitivity to ionizing radiation and some chemical agents
1725:
1523:
and other bacteria in response to extensive DNA damage. The
159:
Paul Modrich talks about himself and his work in DNA repair.
10533:
10489:
10484:
10419:
10414:
10409:
10382:
10362:
10357:
10310:
9756:
9551:"DNA damage, homology-directed repair, and DNA methylation"
8953:
8401:
7513:"DNA damage, homology-directed repair, and DNA methylation"
7315:
6714:
6185:
5080:
3037:
organisms, as well as the presence of potentially damaging
2944:
Homologous recombinational repair alters epigenetic markers
2750:
Repair of oxidative DNA damage can alter epigenetic markers
2736:
2686:
2560:
2556:
1758:
induced by endogenously generated reactive oxygen species.
1747:
1703:
carcinogens and correspondingly increased cancer risk (see
1532:
1528:
1423:
1298:
1294:
1284:
1280:
1193:
1109:. From a cellular perspective, risking the introduction of
1094:
1082:
1031:
967:
909:
81:
6765:
5184:
4676:
3958:. Methods in Enzymology. Vol. 408. pp. 189–213.
3488:
3250:
2450:
1656:
10295:
10290:
8137:
7459:
6609:
6470:
6270:
5132:
1490:
1479:
1449:
1181:
231:
57:
8023:
7653:
6134:
5465:
5416:
3896:
3387:
1950:
pathways and reversion of previously inhibited defects.
1634:, homologous recombination, nucleotide excision repair,
5758:
5729:
1704:
1455:
Checkpoint Proteins can be separated into four groups:
10155:
9648:
9191:
8500:
5230:
2729:-marked regions. Another important mechanism concerns
1863:
All of the above diseases are often called "segmental
10676:
9705:
9383:
9002:
8703:
4804:
4374:
4129:
2586:
the 5 types of DNA damages illustrated in the chart.
1790:
1325:
pathway to enter the chromatin and repair UV-induced
226:
that do not fit in the standard double helix. Unlike
10115:"DNA-damage repair; the good, the bad, and the ugly"
9435:
8901:
3283:
3093:
1754:, and concurrently to reduce constitutive level of
1720:
1448:
and slows down the rate of S phase progression when
1010:
has a remarkable ability to survive DNA damage from
576:
and is condensed into aggregate structures known as
197:
DNA damage, due to environmental factors and normal
9805:
7702:
7208:"Epigenetic field defects in progression to cancer"
6338:Alberts B, Johnson A, Lewis J, et al. (2002).
6337:
5368:
5366:
4980:"Chromatin remodeling, DNA damage repair and aging"
4091:"Modulation of DNA end joining by nuclear proteins"
3999:. New York: W.H. Freeman and Company. p. 840.
3817:
1119:the toxicity and mutagenesis of the same lesion in
1077:post-translational modification of the replication
279:exogenous damage caused by external agents such as
45:
DNA damage resulting in multiple broken chromosomes
9806:Cromie GA, Connelly JC, Leach DR (December 2001).
7460:O'Hagan HM, Mohammad HP, Baylin SB (August 2008).
7156:"Epigenetic changes of DNA repair genes in cancer"
6816:
6083:
5586:
3994:
3213:
1801:
1594:Eukaryotic transcriptional responses to DNA damage
1136:, PCNA is ubiquitinated, or modified, by the RAD6/
254:DNA damage can be subdivided into two main types:
10044:Roswell Park Cancer Institute DNA Repair Lectures
6860:
4805:Colis LC, Raychaudhury P, Basu AK (August 2008).
4278:
2948:At least four articles report the recruitment of
2926:region and the early transcription region of the
1478:An important downstream target of ATM and ATR is
1144:a specialized polymerase is needed to extend it;
1089:mediates error-free bypass of lesions induced by
10700:
9250:
9056:
7195:Epigenetic changes of DNA repair genes in cancer
6917:
6819:"Nucleotide excision repair and human syndromes"
6034:
5688:
5363:
4853:
4517:
3763:
1565:or double-strand breaks, which are processed by
1550:sequences commonly referred to as SOS boxes. In
1151:
1064:machinery to replicate past DNA lesions such as
616:, which is present in both the mitochondria and
510:at 40–80 °C. The rate of depurination (300
481:such as that created by radioactive decay or in
293:) from the sun or other artificial light sources
9925:CBC news. Author Kelly Crowe. 30 November 2015.
9888:The Anatomical Record Part B: The New Anatomist
9881:
9599:
8276:
7112:
6521:
5764:
5508:
5226:
5224:
5222:
4180:
4130:Wilson TE, Grawunder U, Lieber MR (July 1997).
4088:
4084:
4082:
3664:"Nuclear DNA damage as a direct cause of aging"
3322:
2530:Frequencies of epimutations in DNA repair genes
1953:
1845:: sunlight hypersensitivity, high incidence of
1504:
833:(NER): bulky, helix-distorting damage, such as
757:no longer functions in humans, who instead use
636:. The telomeres are long regions of repetitive
551:
469:. The damage caused by free radicals is called
10049:A comprehensive list of Human DNA Repair Genes
8752:
8699:
8697:
8227:
7455:
7453:
7451:
6559:
4235:
3422:
3052:
2952:to sites of DNA double-strand breaks. During
494:at elevated temperature increases the rate of
10224:
9750:
9699:
9642:
9593:
9480:
9377:
9328:
9279:
9244:
9185:
9134:
9085:
8996:
8895:
8586:
8535:
8494:
8445:
8395:
8354:
8319:
8313:
8270:
8080:
7794:
6659:
6657:
6555:
6553:
5950:
5948:
5946:
3953:
2984:The basic processes of DNA repair are highly
2725:proteins, thereby lowering mutation rates in
2714:. One mechanism underlying this involves the
1527:SOS system is regulated by two key proteins:
1267:, to initiate DNA repair, within 13 seconds.
982:(available in G2 after DNA replication) or a
791:Structure of the base-excision repair enzyme
242:and wound around "packaging" proteins called
68:activities and environmental factors such as
10058:
8949:
8947:
8086:
7153:
6560:Jeggo PA, Pearl LH, Carr AM (January 2016).
6364:
5689:Erill I, Campoy S, Barbé J (November 2007).
5459:
5314:
5265:
5219:
4847:
4798:
4749:
4625:
4619:
4570:
4284:
4079:
3607:
3537:
2602:DNA repair pathways appear to be central to
1819:: hypersensitivity to UV and chemical agents
990:and are typically repaired by recombination.
872:The main double-strand break repair pathways
217:The vast majority of DNA damage affects the
112:an irreversible state of dormancy, known as
9846:
8801:
8694:
8643:
8367:International Journal of Molecular Medicine
8360:
7448:
7014:
6861:Broustas CG, Lieberman HB (February 2014).
6346:(4th ed.). New York: Garland Science.
6316:"Unearthing Prehistoric Tumors, and Debate"
5613:
5562:DNA Repair, Genetic Instability, and Cancer
4964:
4962:
4960:
3897:Willey J, Sherwood L, Woolverton C (2014).
3381:
2902:with agents causing oxidative DNA damage, (
2467:(hypermethylation and hypomethylation) and
1301:. This complex further complexes with the
623:
600:, byproducts of the constant production of
10231:
10217:
9544:
9542:
9285:
7212:World Journal of Gastrointestinal Oncology
6654:
6550:
6370:
6077:
5943:
4977:
4762:Microbiology and Molecular Biology Reviews
4451:|...|intentional=yes}}
4186:
4045:Journal of the American Geriatrics Society
3949:
3947:
3945:
3943:
3350:
2765:(a cytosine followed by guanine along its
2701:for summary), and are also shown in cyan.
2658:
2595:
928:, the process that generates diversity in
709:
10247:
10191:
10181:
10138:
10076:
9899:
9823:
9782:
9733:
9723:
9682:
9625:
9576:
9566:
9522:
9512:
9463:
9453:
9431:
9429:
9409:
9360:
9311:
9227:
9217:
9168:
9158:
9117:
9028:
8979:
8944:
8927:
8878:
8829:
8819:
8778:
8729:
8677:
8620:
8610:
8569:
8559:
8518:
8477:
8378:
8337:
8253:
8204:
8163:
8114:
8051:
8041:
8000:
7990:
7941:
7856:
7771:
7761:
7720:
7679:
7587:
7538:
7528:
7487:
7477:
7431:
7390:
7341:
7292:
7282:
7233:
7223:
7179:
7130:
7089:
7040:
6968:
6945:
6935:
6894:
6837:
6447:
6398:
6388:
6239:
6060:
5958:
5874:
5825:
5706:
5662:
5584:
5559:
5442:
5390:
5346:
5289:
5248:
5202:
5180:
5178:
5158:
5106:
5076:
5074:
5072:
5052:
5003:
4879:
4830:
4781:
4653:
4643:
4602:
4553:
4543:
4513:
4511:
4483:
4400:
4351:
4325:
4302:
4261:
4236:Boulton SJ, Jackson SP (September 1996).
4212:
4155:
4106:
4036:
4022:Johns Hopkins Medical Journal. Supplement
3892:
3890:
3888:
3813:
3811:
3809:
3789:
3682:
3555:
3514:
3473:
3297:
3255:(5th ed.). WH Freeman. p. 963.
1900:Hereditary nonpolyposis colorectal cancer
1362:
10054:3D structures of some DNA repair enzymes
10015:, and does not reflect subsequent edits.
9998:
9875:
9288:"DNA methylation and its basic function"
9052:
9050:
9048:
8592:
8541:
8017:
7709:Journal of the National Cancer Institute
6817:de Boer J, Hoeijmakers JH (March 2000).
6307:
5991:
5985:
5684:
5682:
5412:
5410:
4957:
3441:
3246:
3244:
2771:
2737:Epigenetic alterations due to DNA repair
2533:
1825:: sensitive skin, brittle hair and nails
1724:
1660:
1123:by replicating a GT-modified plasmid in
1055:
894:
867:
786:
145:
52:is a collection of processes by which a
40:
9882:Maresca B, Schwartz JH (January 2006).
9840:
9799:
9539:
9091:
6313:
6179:
5793:
5723:
5128:
5126:
4978:Liu B, Yip RK, Zhou Z (November 2012).
4906:. Research.chem.psu.edu. Archived from
4670:
4465:
4019:
4013:
3940:
3921:
3843:Environmental and Molecular Mutagenesis
3840:
3834:
3657:
3655:
3653:
3427:(11th ed.). Pearson. p. 136.
2499:instability characteristic of cancers.
2487:. These changes usually remain through
2451:Epigenetic DNA repair defects in cancer
1750:signaling, an evidence of reduction of
1657:Pathological effects of poor DNA repair
1297:occurs in a heterodimeric complex with
916:that forms a complex with the cofactor
863:
782:
296:other radiation frequencies, including
14:
10701:
10059:Machado CR, Menck CF (December 1997).
9426:
9286:Moore LD, Le T, Fan G (January 2013).
8221:
7610:
7561:
7413:
6264:
6215:
5842:
5779:10.1146/annurev.micro.59.031805.133658
5644:
5638:
5175:
5069:
4854:Raychaudhury P, Basu AK (March 2011).
4508:
3901:. New York: McGraw Hill. p. 381.
3885:
3806:
3728:
3722:
3616:Nature Reviews. Molecular Cell Biology
3277:
2954:homologous recombinational repair (HR)
960:flap structure-specific endonuclease 1
532:, and environmental chemicals such as
56:identifies and corrects damage to the
10212:
10112:
9045:
8593:Bi FF, Li D, Yang Q (February 2013).
8089:Epigenetic Alterations in Oncogenesis
7154:Lahtz C, Pfeifer GP (February 2011).
6128:
5899:
5679:
5407:
3995:Berg M, Tymoczko J, Stryer L (2012).
3578:
3572:
3531:
3356:
3328:
3241:
3226:Nature Reviews Molecular Cell Biology
1839:: premature aging and retarded growth
1263:recruitment of the DNA repair enzyme
1212:The packaging of eukaryotic DNA into
572:during non-replicative stages of the
439:causes crosslinking between adjacent
7113:Jacinto FV, Esteller M (July 2007).
7017:"Epigenetic modifications in cancer"
5994:Mechanisms of Ageing and Development
5123:
4928:
4368:
4285:Wilson TE, Lieber MR (August 1999).
3988:
3764:Lucas-Lledó JI, Lynch M (May 2009).
3661:
3650:
3065:cell that will eventually produce a
2850:, one particular gene was examined,
1832:Other DNA repair disorders include:
1072:. It involves switching out regular
5237:The Journal of Biological Chemistry
5191:The Journal of Biological Chemistry
4971:
4291:The Journal of Biological Chemistry
4095:The Journal of Biological Chemistry
3221:"Nature Reviews Series: DNA damage"
2433:
2420:
2411:
2397:
2388:
2381:
2372:
2356:
2345:
2329:
2322:
2315:
2293:
2286:
2264:
2257:
2244:
2226:
2215:
2197:
2186:
2166:
2155:
2139:
2128:
2119:
2097:
2090:
2070:
2063:
2056:
2036:
2029:
2022:
24:
10539:Proliferating Cell Nuclear Antigen
10470:Microhomology-mediated end joining
9985:
8361:Wang K, Xie C, Chen D (May 2014).
7420:American Journal of Human Genetics
6340:"The Preventable Causes of Cancer"
4254:10.1002/j.1460-2075.1996.tb00890.x
4057:10.1111/j.1532-5415.1971.tb02577.x
3538:Braig M, Schmitt CA (March 2006).
2674:microhomology-mediated end joining
2672:Cyan-highlighted genes are in the
1917:Cancer therapy procedures such as
1791:Medicine and DNA repair modulation
1465:proliferating cell nuclear antigen
1270:γH2AX, the phosphorylated form of
1130:Proliferating cell nuclear antigen
886:microhomology-mediated end joining
719:
25:
10740:
10086:DNA repair special interest group
9932:
8458:The American Journal of Pathology
7750:World Journal of Gastroenterology
7160:Journal of Molecular Cell Biology
6536:10.1146/annurev-med-081313-121208
5614:Gartel AL, Tyner AL (June 2002).
4326:Budman J, Chu G (February 2005).
3926:. Chennai: Pearson. p. 186.
2669:would be carcinogenic in itself.
1721:Longevity and caloric restriction
1488:cyclin-dependent kinase inhibitor
1482:, as it is required for inducing
10686:
10661:
10660:
10554:Meiotic recombination checkpoint
10031:
9997:
9916:
8846:
8795:
8746:
8637:
8291:10.1111/j.1464-410X.2006.06224.x
8180:
8131:
8068:
7958:
7917:
7873:
7832:
7798:Langenbeck's Archives of Surgery
7788:
7737:
7696:
7647:
7604:
7555:
7033:10.1111/j.1399-0004.2011.01809.x
7015:Kanwal R, Gupta S (April 2012).
6440:10.1016/j.pharmthera.2016.02.003
5708:10.1111/j.1574-6976.2007.00082.x
3286:The American Journal of Medicine
3128:DNA damage (naturally occurring)
3096:
2870:While six-hour incubation with H
2856:. The methylation level of the
2744:DNA damage (naturally occurring)
2434:
2421:
2412:
2398:
2389:
2382:
2373:
2357:
2346:
2330:
2323:
2316:
2294:
2287:
2265:
2258:
2245:
2227:
2216:
2198:
2187:
2167:
2156:
2140:
2129:
2120:
2098:
2091:
2071:
2064:
2057:
2037:
2030:
2023:
1207:
568:. Nuclear DNA (n-DNA) exists as
534:polycyclic aromatic hydrocarbons
189:DNA damage (naturally occurring)
10078:10.1590/S0100-84551997000400032
8802:Supek F, Lehner B (July 2017).
7504:
7407:
7358:
7309:
7250:
7199:
7147:
7106:
7082:10.1128/MCB.23.7.2225-2238.2003
7057:
7008:
6962:
6911:
6854:
6810:
6759:
6708:
6603:
6515:
6464:
6428:Pharmacology & Therapeutics
6415:
6331:
6028:
5607:
5578:
5553:
5502:
5020:
4922:
4896:
4721:
4466:Jung D, Alt FW (January 2004).
4459:
4319:
4229:
4187:Moore JK, Haber JE (May 1996).
4123:
3915:
3770:Molecular Biology and Evolution
3757:
3425:Brock Biology of Microorganisms
3423:Madigan MT, Martino JM (2006).
2950:DNA methyltransferase 1 (DNMT1)
2742:somatic replicating cells (see
2609:The two gray-highlighted genes
1802:Hereditary DNA repair disorders
1245:post-translational modification
10238:
8644:Supek F, Lehner B (May 2015).
7070:Molecular and Cellular Biology
6314:Johnson G (28 December 2010).
5589:Checkpoint Controls and Cancer
4193:Molecular and Cellular Biology
3482:
3416:
3402:10.1146/annurev.micro.53.1.577
3148:Error detection and correction
2520:DNA repair-deficiency disorder
1797:DNA repair-deficiency disorder
956:Poly (ADP-ribose) polymerase 1
64:. In human cells, both normal
13:
1:
9825:10.1016/S1097-2765(01)00419-1
9265:10.1016/j.cellsig.2016.05.021
9071:10.1016/j.cellsig.2016.05.021
8548:BioMed Research International
8470:10.1016/S0002-9440(10)63911-9
8246:10.1158/1541-7786.MCR-08-0269
7858:10.1158/1078-0432.CCR-12-3518
7633:10.1126/science.278.5340.1043
6344:Molecular biology of the cell
6201:10.1016/S1568-7864(02)00219-7
5767:Annual Review of Microbiology
5620:Molecular Cancer Therapeutics
5087:Molecular Biology of the Cell
4943:10.1016/S0921-8777(01)00089-1
4485:10.1016/S0092-8674(04)00039-X
4416:(This paper currently has an
3964:10.1016/S0076-6879(06)08012-8
3820:Molecular Biology of the Gene
3557:10.1158/0008-5472.CAN-05-4006
3390:Annual Review of Microbiology
3206:
3077:
2571:, which down-regulates MLH1.
1980:) have a higher cancer risk.
1469:Ataxia telangiectasia mutated
1457:phosphatidylinositol 3-kinase
1237:c-Jun N-terminal kinase (JNK)
1152:Global response to DNA damage
946:MMEJ starts with short-range
689:
182:
10436:Transcription-coupled repair
10183:10.1371/journal.pone.0151367
9963:Resources in other libraries
9568:10.1371/journal.pgen.0030110
8722:10.1016/j.celrep.2014.10.031
8542:Bi FF, Li D, Yang Q (2013).
8423:10.1016/j.canlet.2004.10.035
7943:10.1053/j.gastro.2005.01.056
7530:10.1371/journal.pgen.0030110
7479:10.1371/journal.pgen.1000155
6371:Friedenson B (August 2007).
5929:10.1016/j.mrfmmm.2005.11.008
5560:Wei Q, Li L, Chen D (2007).
5151:10.1016/j.celrep.2016.08.006
3308:10.1016/j.amjmed.2004.06.033
3158:Human mitochondrial genetics
2979:
1954:DNA repair defects in cancer
1761:For example, increasing the
1505:The prokaryotic SOS response
1327:cyclobutane pyrimidine dimer
1256:adenosine diphosphate ribose
552:Nuclear versus mitochondrial
210:formation and contribute to
118:cell suicide, also known as
7:
8097:10.1007/978-1-4419-9967-2_1
7383:10.1093/embo-reports/kvf037
5423:The Journal of Cell Biology
4738:10.1667/0033-7587(2003)159
3329:Broad WJ (7 October 2015).
3089:
3053:Rate of evolutionary change
2794:8-hydroxy-2'-deoxyguanosine
2435:
2422:
2413:
2399:
2390:
2383:
2374:
2358:
2347:
2331:
2324:
2317:
2295:
2288:
2266:
2259:
2246:
2228:
2217:
2199:
2188:
2168:
2157:
2141:
2130:
2121:
2099:
2092:
2072:
2065:
2058:
2038:
2031:
2024:
1785:biological origins of aging
1438:signal transduction pathway
663:
416:of bases, due to errors in
10:
10745:
10458:Non-homologous end joining
10282:Nucleotide excision repair
10275:Poly ADP ribose polymerase
9725:10.1186/s12864-020-07233-2
9110:10.1016/j.csbj.2019.12.013
9098:Comput Struct Biotechnol J
8821:10.1016/j.cell.2017.07.003
8771:10.1016/j.cell.2013.03.025
8339:10.1158/1078-0432.473.11.2
5291:10.1016/j.cell.2007.09.040
4996:10.2174/138920212803251373
3133:DNA damage theory of aging
2974:Non-homologous end joining
2731:nucleotide excision repair
2623:homologous recombinational
2509:homologous recombinational
1869:accelerated aging diseases
1794:
1652:DNA damage theory of aging
1649:
1486:following DNA damage. The
1444:progression in G1, G2 and
1323:nucleotide excision repair
1200:arrest, and inhibition of
882:non-homologous end joining
831:Nucleotide excision repair
759:nucleotide excision repair
693:
329:compounds that act as DNA
249:
193:Free radical damage to DNA
186:
60:molecules that encode its
31:
10656:
10521:
10500:
10428:
10373:
10246:
10113:Hakem R (February 2008).
10103:DNA Damage and DNA Repair
9958:Resources in your library
9775:10.18632/oncotarget.16122
8234:Molecular Cancer Research
7895:10.1007/s11033-012-2465-3
7883:Molecular Biology Reports
7810:10.1007/s00423-011-0812-9
6524:Annual Review of Medicine
6006:10.1016/j.mad.2005.03.016
5695:FEMS Microbiology Reviews
3113:Accelerated aging disease
3043:oxidative phosphorylation
1889:
1230:histone-modifying enzymes
1103:Watson-Crick base pairing
1022:regions through a moving
606:oxidative phosphorylation
261:damage such as attack by
10453:Homology directed repair
10375:Homologous recombination
10096:12 February 2018 at the
9493:Proc Natl Acad Sci U S A
9198:Proc Natl Acad Sci U S A
8326:Clinical Cancer Research
7845:Clinical Cancer Research
7763:10.3748/wjg.v16.i28.3553
7580:10.1177/1947601911413466
5818:10.1038/sj.embor.7400127
5651:Acta Biochimica Polonica
4732:2003 Apr;159(4):502–10.
4645:10.3389/fgene.2013.00048
4583:Cell Death & Disease
4344:10.1038/sj.emboj.7600563
4304:10.1074/jbc.274.33.23599
3997:Biochemistry 7th edition
3357:Staff (7 October 2015).
2479:) and changes caused by
1939:homologous recombination
1645:
1611:Saccharomyces cerevisiae
1414:downstream targets in a
1036:homologous recombination
890:homologous recombination
624:Senescence and apoptosis
408:"bulky adduct formation"
381:), such as formation of
355:
165:Nobel Prize in Chemistry
9514:10.1073/pnas.0501034102
9292:Neuropsychopharmacology
9219:10.1073/pnas.0406048101
8612:10.1186/1471-2407-13-90
7992:10.1073/pnas.1002472107
7672:10.1136/gut.2004.059535
7562:Malkin D (April 2011).
7414:German J (March 1969).
6839:10.1093/carcin/21.3.453
6788:10.1126/science.1140735
6390:10.1186/1471-2407-7-152
6157:10.1126/science.1099196
5876:10.1126/science.1070174
5379:Journal of Cell Science
5250:10.1074/jbc.273.10.5858
5099:10.1091/mbc.E16-05-0269
4904:"Translesion Synthesis"
4626:Decottignies A (2013).
4545:10.1073/pnas.1213431110
3899:Prescott's Microbiology
3192:The scientific journal
2756:8-oxo-2'-deoxyguanosine
2548:in the DNA repair gene
1742:pathways and decreased
1710:Deinococcus radiodurans
1499:cyclin-dependent kinase
1007:Deinococcus radiodurans
835:pyrimidine dimerization
671:8-hydroxydeoxyguanosine
594:reactive oxygen species
404:, and depyrimidination.
348:, for example, through
263:reactive oxygen species
10475:Postreplication repair
10270:Uracil-DNA glycosylase
9993:
9973:Listen to this article
8972:10.1093/nar/29.10.2117
8520:10.1038/sj.onc.1206977
8380:10.3892/ijmm.2014.1682
8156:10.1261/rna.034926.112
8075:Human DNA Repair Genes
7564:"Li-fraumeni syndrome"
7284:10.1073/pnas.94.7.3122
6974:Nature Reviews. Cancer
6937:10.1186/1476-4598-3-14
6717:Nature Reviews. Cancer
6569:Nature Reviews. Cancer
5664:10.18388/abp.2001_3894
5339:10.1038/emboj.2012.104
5204:10.1074/jbc.M706734200
4381:Nucleic Acids Research
4108:10.1074/jbc.M503776200
3593:10.1089/dna.2006.25.69
3253:Molecular Cell Biology
2814:Oxoguanine glycosylase
2809:
2540:
2458:epigenetic alterations
1768:Caenorhabditis elegans
1730:
1666:
1632:postreplication repair
1363:DNA damage checkpoints
1107:Hoogsteen base pairing
904:
873:
796:
793:uracil-DNA glycosylase
602:adenosine triphosphate
204:tumor suppressor genes
160:
46:
10131:10.1038/emboj.2008.15
9992:
8920:10.1093/toxsci/kfq371
8043:10.1186/2041-9414-3-3
7334:10.1093/carcin/bgl079
7225:10.4251/wjgo.v5.i3.43
7132:10.1093/mutage/gem009
6241:10.1096/fj.03-0890fje
6053:10.18632/aging.100521
5585:Schonthal AH (2004).
5435:10.1083/jcb.201112132
4774:10.1128/MMBR.00034-08
4632:Frontiers in Genetics
4595:10.1038/cddis.2015.58
4449:expression of concern
4443:|...}}
4441:expression of concern
4418:expression of concern
4205:10.1128/mcb.16.5.2164
3863:10.1002/em.2850110210
3782:10.1093/molbev/msp029
3693:10.1089/rej.2009.0847
3671:Rejuvenation Research
3662:Best BP (June 2009).
3454:Genes and Environment
2920:DNA methyltransferase
2898:Jiang et al. treated
2775:
2659:translesion synthesis
2596:translesion synthesis
2537:
1857:Ataxia telangiectasia
1811:Xeroderma pigmentosum
1728:
1664:
1636:DNA damage checkpoint
1603:cell cycle checkpoint
1434:DNA damage checkpoint
1390:boundaries. An intra-
1056:Translesion synthesis
984:homologous chromosome
976:chromosomal crossover
898:
878:genome rearrangements
871:
790:
710:translesion synthesis
620:of eukaryotic cells.
540:, just to name a few.
504:thermophilic bacteria
309:or thermal disruption
267:oxidative deamination
187:Further information:
158:
124:programmed cell death
44:
32:For the journal, see
10581:core protein complex
10256:Base excision repair
10040:at Wikimedia Commons
10024:More spoken articles
9455:10.3390/cells9010225
9304:10.1038/npp.2012.112
9160:10.3390/ijms21218360
8914:(Suppl 1): S130–45.
8859:Nature Biotechnology
8206:10.1038/onc.2011.660
5967:Uchu Seibutsu Kagaku
5564:. World Scientific.
5045:10.4161/cc.8.14.8984
3581:DNA and Cell Biology
3507:10.4161/cc.5.17.3191
3475:10.3123/jemsge.28.56
2912:Base excision repair
2798:base excision repair
2721:, which can recruit
2716:histone modification
2469:histone modification
1978:Li-Fraumeni syndrome
1334:chromatin remodeling
1226:chromatin remodeling
864:Double-strand breaks
809:Base excision repair
783:Single-strand damage
614:superoxide dismutase
612:of these species is
556:In human cells, and
522:Industrial chemicals
518:cannot be ruled out.
331:intercalating agents
234:, DNA usually lacks
34:DNA Repair (journal)
18:Double-strand breaks
10353:DNA mismatch repair
10174:2016PLoSO..1151367M
9769:(25): 40359–40372.
9667:2016NatSR...633222R
9505:2005PNAS..102.8905M
9402:10.1093/jmcb/mjv050
9210:2004PNAS..10113738L
9092:Poetsch AR (2020).
8670:10.1038/nature14173
8662:2015Natur.521...81S
8561:10.1155/2013/946268
7983:2010PNAS..107.6982V
7722:10.1093/jnci/dji275
7625:1997Sci...278.1043F
7275:1997PNAS...94.3122N
7172:10.1093/jmcb/mjq053
6879:2014RadR..181..111B
6780:2008Sci...319.1352H
6686:10.1038/nature05268
6678:2006Natur.444..633B
6632:10.1038/nature03482
6624:2005Natur.434..864B
6493:10.1038/nature03443
6485:2005Natur.434..913B
6149:2004Sci...305..390C
6098:2001Natur.410..227T
5921:2006MRFMM.596...22D
5867:2002Sci...296.1276D
5531:10.1038/nature01368
5523:2003Natur.421..499B
5468:Nature Cell Biology
4699:10.1038/nature05160
4691:2006Natur.443..569Z
4536:2013PNAS..110.7720T
4426:10.1093/nar/gkaa228
4148:1997Natur.388..495W
3855:1988EnvMM..11..241V
3710:on 15 November 2017
3466:2006GeneE..28...56O
3163:Indirect DNA damage
3041:in the cell due to
2621:, are required for
2505:DNA mismatch repair
2447:
1823:Trichothiodystrophy
1736:Caloric restriction
1416:signal transduction
926:V(D)J recombination
538:crosslinking of DNA
471:indirect DNA damage
385:, 1-methyladenine,
323:mutagenic chemicals
212:tumor heterogeneity
10719:Molecular genetics
10714:Cellular processes
10108:Segmental Progeria
9994:
9901:10.1002/ar.b.20089
9618:10.1093/hmg/ddq451
8814:(3): 534–547.e23.
8332:(2 Pt 1): 473–82.
7568:Genes & Cancer
6867:Radiation Research
6581:10.1038/nrc.2015.4
6321:The New York Times
5955:PMID 26729707
5392:10.1242/jcs.008367
5385:(Pt 15): 2706–16.
4393:10.1093/nar/gkg728
3956:DNA Repair, Part A
3922:Russell P (2018).
3336:The New York Times
3031:oxygen catastrophe
2908:potassium chromate
2810:
2541:
2524:germline mutations
2442:
1961:Replication stress
1752:metabolic activity
1731:
1680:maximum life spans
1667:
1513:is the changes in
1367:After DNA damage,
1220:. In eukaryotes,
1158:ionizing radiation
1012:ionizing radiation
905:
874:
819:). Enzymes called
797:
712:as a last resort.
654:cellular signaling
492:Thermal disruption
478:Ionizing radiation
396:of bases, such as
377:of bases (usually
273:replication errors
236:tertiary structure
161:
102:two-hit hypothesis
47:
27:Cellular mechanism
10674:
10673:
10549:Adaptive response
10036:Media related to
9990:
9939:Library resources
9861:10.1021/cr040481v
9675:10.1038/srep33222
9021:10.1021/ja411636j
8960:Nucleic Acids Res
8279:BJU International
8106:978-1-4419-9966-5
7619:(5340): 1043–50.
7021:Clinical Genetics
6887:10.1667/RR13515.1
6774:(5868): 1352–55.
6353:978-0-8153-4072-0
5909:Mutation Research
5861:(5571): 1276–79.
5744:10.1021/cr0404951
5645:Janion C (2001).
5600:978-1-58829-500-2
5571:978-981-270-014-8
5517:(6922): 499–506.
4931:Mutation Research
4872:10.1021/bi102064z
4823:10.1021/bi800529f
4297:(33): 23599–609.
4006:978-1-4292-2936-4
3973:978-0-12-182813-4
3933:978-93-325-7162-4
3908:978-0-07-340240-6
3743:10.1021/cr0204348
3434:978-0-13-196893-6
3262:978-0-7167-4366-8
3199:Mutation Research
3143:Direct DNA damage
3010:structural motifs
2904:potassium bromate
2778:DNA demethylation
2767:5' → 3' direction
2710:late-replicating
2546:missense mutation
2448:
2441:
1970:short hairpin RNA
1837:Werner's syndrome
1817:Cockayne syndrome
1563:replication forks
1408:replication forks
1239:, phosphorylates
1186:replication forks
1162:ultraviolet light
1156:Cells exposed to
776:adaptive response
741:(300–500 nm
731:photoreactivation
727:pyrimidine dimers
530:hydrogen peroxide
516:adaptive response
455:direct DNA damage
453:. This is called
450:pyrimidine dimers
387:6-O-Methylguanine
383:7-methylguanosine
219:primary structure
156:
74:molecular lesions
16:(Redirected from
10736:
10691:
10690:
10682:
10664:
10663:
10233:
10226:
10219:
10210:
10209:
10205:
10195:
10185:
10152:
10142:
10082:
10080:
10035:
10014:
10012:
10001:
10000:
9991:
9981:
9979:
9974:
9926:
9920:
9914:
9913:
9903:
9879:
9873:
9872:
9849:Chemical Reviews
9844:
9838:
9837:
9827:
9803:
9797:
9796:
9786:
9754:
9748:
9747:
9737:
9727:
9703:
9697:
9696:
9686:
9646:
9640:
9639:
9629:
9597:
9591:
9590:
9580:
9570:
9546:
9537:
9536:
9526:
9516:
9484:
9478:
9477:
9467:
9457:
9433:
9424:
9423:
9413:
9381:
9375:
9374:
9364:
9353:10.1038/nbt.2726
9332:
9326:
9325:
9315:
9283:
9277:
9276:
9259:(9): 1163–1171.
9248:
9242:
9241:
9231:
9221:
9204:(38): 13738–43.
9189:
9183:
9182:
9172:
9162:
9138:
9132:
9131:
9121:
9089:
9083:
9082:
9065:(9): 1163–1171.
9054:
9043:
9042:
9032:
9000:
8994:
8993:
8983:
8951:
8942:
8941:
8931:
8899:
8893:
8892:
8882:
8871:10.1038/nbt.2778
8850:
8844:
8843:
8833:
8823:
8799:
8793:
8792:
8782:
8750:
8744:
8743:
8733:
8701:
8692:
8691:
8681:
8641:
8635:
8634:
8624:
8614:
8590:
8584:
8583:
8573:
8563:
8539:
8533:
8532:
8522:
8498:
8492:
8491:
8481:
8449:
8443:
8442:
8408:
8399:
8393:
8392:
8382:
8358:
8352:
8351:
8341:
8317:
8311:
8310:
8274:
8268:
8267:
8257:
8225:
8219:
8218:
8208:
8184:
8178:
8177:
8167:
8135:
8129:
8128:
8118:
8084:
8078:
8072:
8066:
8065:
8055:
8045:
8030:Genome Integrity
8021:
8015:
8014:
8004:
7994:
7962:
7956:
7955:
7945:
7930:Gastroenterology
7921:
7915:
7914:
7877:
7871:
7870:
7860:
7836:
7830:
7829:
7792:
7786:
7785:
7775:
7765:
7741:
7735:
7734:
7724:
7700:
7694:
7693:
7683:
7651:
7645:
7644:
7608:
7602:
7601:
7591:
7559:
7553:
7552:
7542:
7532:
7508:
7502:
7501:
7491:
7481:
7457:
7446:
7445:
7435:
7411:
7405:
7404:
7394:
7362:
7356:
7355:
7345:
7313:
7307:
7306:
7296:
7286:
7254:
7248:
7247:
7237:
7227:
7203:
7197:
7193:
7183:
7151:
7145:
7144:
7134:
7110:
7104:
7103:
7093:
7061:
7055:
7054:
7044:
7012:
7006:
7005:
6966:
6960:
6959:
6949:
6939:
6924:Molecular Cancer
6915:
6909:
6908:
6898:
6858:
6852:
6851:
6841:
6823:
6814:
6808:
6807:
6763:
6757:
6756:
6712:
6706:
6705:
6672:(7119): 633–37.
6661:
6652:
6651:
6618:(7035): 864–70.
6607:
6601:
6600:
6566:
6557:
6548:
6547:
6519:
6513:
6512:
6479:(7035): 913–17.
6468:
6462:
6461:
6451:
6419:
6413:
6412:
6402:
6392:
6368:
6362:
6361:
6335:
6329:
6328:
6311:
6305:
6304:
6285:10.1038/35012693
6279:(6784): 296–97.
6268:
6262:
6261:
6243:
6219:
6213:
6212:
6183:
6177:
6176:
6143:(5682): 390–92.
6132:
6126:
6125:
6106:10.1038/35065638
6092:(6825): 227–30.
6081:
6075:
6074:
6064:
6032:
6026:
6025:
5989:
5983:
5982:
5962:
5956:
5952:
5941:
5940:
5903:
5897:
5896:
5878:
5846:
5840:
5839:
5829:
5797:
5791:
5790:
5762:
5756:
5755:
5732:Chemical Reviews
5727:
5721:
5720:
5710:
5686:
5677:
5676:
5666:
5642:
5636:
5635:
5611:
5605:
5604:
5593:. Humana Press.
5592:
5582:
5576:
5575:
5557:
5551:
5550:
5506:
5500:
5499:
5463:
5457:
5456:
5446:
5414:
5405:
5404:
5394:
5370:
5361:
5360:
5350:
5327:The EMBO Journal
5318:
5312:
5311:
5293:
5269:
5263:
5262:
5252:
5228:
5217:
5216:
5206:
5182:
5173:
5172:
5162:
5130:
5121:
5120:
5110:
5078:
5067:
5066:
5056:
5024:
5018:
5017:
5007:
4984:Current Genomics
4975:
4969:
4966:
4955:
4954:
4926:
4920:
4919:
4917:
4915:
4910:on 10 March 2012
4900:
4894:
4893:
4883:
4851:
4845:
4844:
4834:
4802:
4796:
4795:
4785:
4753:
4747:
4725:
4719:
4718:
4685:(7111): 569–73.
4674:
4668:
4667:
4657:
4647:
4623:
4617:
4616:
4606:
4574:
4568:
4567:
4557:
4547:
4515:
4506:
4505:
4487:
4463:
4457:
4456:
4454:
4452:
4444:
4414:
4404:
4372:
4366:
4365:
4355:
4332:The EMBO Journal
4323:
4317:
4316:
4306:
4282:
4276:
4275:
4265:
4248:(18): 5093–103.
4242:The EMBO Journal
4233:
4227:
4226:
4216:
4184:
4178:
4177:
4159:
4127:
4121:
4120:
4110:
4101:(36): 31442–49.
4086:
4077:
4076:
4040:
4034:
4033:
4017:
4011:
4010:
3992:
3986:
3985:
3951:
3938:
3937:
3919:
3913:
3912:
3894:
3883:
3882:
3838:
3832:
3831:
3815:
3804:
3803:
3793:
3761:
3755:
3754:
3731:Chemical Reviews
3726:
3720:
3719:
3717:
3715:
3709:
3703:. Archived from
3686:
3668:
3659:
3648:
3647:
3611:
3605:
3604:
3576:
3570:
3569:
3559:
3535:
3529:
3528:
3518:
3486:
3480:
3479:
3477:
3445:
3439:
3438:
3420:
3414:
3413:
3385:
3379:
3378:
3376:
3374:
3363:
3354:
3348:
3347:
3345:
3343:
3326:
3320:
3319:
3301:
3281:
3275:
3274:
3248:
3239:
3238:
3236:
3234:
3217:
3106:
3101:
3100:
3047:oxidative stress
2790:5-methylcytosine
2544:only four had a
2446:
2438:
2437:
2425:
2424:
2416:
2415:
2402:
2401:
2393:
2392:
2386:
2385:
2377:
2376:
2361:
2360:
2350:
2349:
2334:
2333:
2327:
2326:
2320:
2319:
2298:
2297:
2291:
2290:
2269:
2268:
2262:
2261:
2249:
2248:
2231:
2230:
2220:
2219:
2202:
2201:
2191:
2190:
2171:
2170:
2160:
2159:
2144:
2143:
2133:
2132:
2124:
2123:
2102:
2101:
2095:
2094:
2075:
2074:
2068:
2067:
2061:
2060:
2041:
2040:
2034:
2033:
2027:
2026:
1992:
1991:
1843:Bloom's syndrome
1740:nutrient sensing
1583:Escherichia coli
1553:Escherichia coli
1520:Escherichia coli
1410:. These kinases
1303:ubiquitin ligase
1121:Escherichia coli
988:replication fork
934:T-cell receptors
912:, a specialized
821:AP endonucleases
644:). In contrast,
506:, which grow in
426:Di adduct damage
157:
21:
10744:
10743:
10739:
10738:
10737:
10735:
10734:
10733:
10699:
10698:
10697:
10685:
10677:
10675:
10670:
10652:
10522:Other/ungrouped
10517:
10496:
10424:
10369:
10265:DNA glycosylase
10248:Excision repair
10242:
10237:
10168:(3): e0151367.
10098:Wayback Machine
10028:
10027:
10016:
10010:
10008:
10005:This audio file
10002:
9995:
9986:
9983:
9977:
9976:
9972:
9969:
9968:
9967:
9947:
9946:
9942:
9935:
9930:
9929:
9921:
9917:
9880:
9876:
9845:
9841:
9804:
9800:
9755:
9751:
9704:
9700:
9647:
9643:
9598:
9594:
9547:
9540:
9485:
9481:
9434:
9427:
9390:J Mol Cell Biol
9382:
9378:
9347:(12): 1137–42.
9341:Nat. Biotechnol
9333:
9329:
9284:
9280:
9249:
9245:
9190:
9186:
9139:
9135:
9090:
9086:
9055:
9046:
9015:(11): 4223–35.
9001:
8997:
8966:(10): 2117–26.
8952:
8945:
8900:
8896:
8851:
8847:
8800:
8796:
8751:
8747:
8702:
8695:
8656:(7550): 81–84.
8642:
8638:
8591:
8587:
8540:
8536:
8513:(46): 7243–46.
8499:
8495:
8450:
8446:
8406:
8400:
8396:
8359:
8355:
8318:
8314:
8275:
8271:
8240:(11): 1710–17.
8226:
8222:
8199:(49): 5108–16.
8185:
8181:
8136:
8132:
8107:
8085:
8081:
8073:
8069:
8022:
8018:
7977:(15): 6982–87.
7963:
7959:
7922:
7918:
7878:
7874:
7837:
7833:
7793:
7789:
7756:(28): 3553–60.
7742:
7738:
7715:(18): 1330–38.
7701:
7697:
7652:
7648:
7609:
7605:
7560:
7556:
7509:
7505:
7472:(8): e1000155.
7458:
7449:
7412:
7408:
7363:
7359:
7328:(12): 2402–08.
7314:
7310:
7255:
7251:
7204:
7200:
7152:
7148:
7111:
7107:
7062:
7058:
7013:
7009:
6986:10.1038/nrc1799
6967:
6963:
6916:
6912:
6859:
6855:
6821:
6815:
6811:
6764:
6760:
6729:10.1038/nrc3916
6713:
6709:
6662:
6655:
6608:
6604:
6564:
6558:
6551:
6520:
6516:
6469:
6465:
6420:
6416:
6369:
6365:
6354:
6336:
6332:
6312:
6308:
6269:
6265:
6220:
6216:
6184:
6180:
6133:
6129:
6082:
6078:
6033:
6029:
5990:
5986:
5963:
5959:
5953:
5944:
5904:
5900:
5847:
5843:
5798:
5794:
5763:
5759:
5728:
5724:
5687:
5680:
5643:
5639:
5612:
5608:
5601:
5583:
5579:
5572:
5558:
5554:
5507:
5503:
5480:10.1038/ncb1337
5464:
5460:
5415:
5408:
5371:
5364:
5333:(11): 2511–27.
5319:
5315:
5270:
5266:
5243:(10): 5858–68.
5229:
5220:
5197:(2): 1197–208.
5183:
5176:
5145:(10): 2641–50.
5131:
5124:
5079:
5070:
5025:
5021:
4976:
4972:
4967:
4958:
4927:
4923:
4913:
4911:
4902:
4901:
4897:
4852:
4848:
4803:
4799:
4754:
4750:
4726:
4722:
4675:
4671:
4624:
4620:
4575:
4571:
4516:
4509:
4464:
4460:
4446:
4438:
4436:
4415:
4387:(18): 5377–88.
4373:
4369:
4324:
4320:
4283:
4279:
4234:
4230:
4185:
4181:
4142:(6641): 495–8.
4128:
4124:
4087:
4080:
4041:
4037:
4018:
4014:
4007:
3993:
3989:
3974:
3952:
3941:
3934:
3920:
3916:
3909:
3895:
3886:
3839:
3835:
3816:
3807:
3762:
3758:
3727:
3723:
3713:
3711:
3707:
3666:
3660:
3651:
3628:10.1038/nrm2233
3612:
3608:
3577:
3573:
3544:Cancer Research
3536:
3532:
3501:(17): 1940–45.
3487:
3483:
3446:
3442:
3435:
3421:
3417:
3386:
3382:
3372:
3370:
3361:
3355:
3351:
3341:
3339:
3327:
3323:
3299:10.1.1.556.6874
3282:
3278:
3263:
3249:
3242:
3232:
3230:
3219:
3218:
3214:
3209:
3204:
3138:DNA replication
3102:
3095:
3092:
3080:
3055:
2996:and even among
2982:
2971:
2946:
2916:polymerase beta
2893:
2889:
2885:
2881:
2877:
2873:
2867:messenger RNA.
2849:
2845:
2837:
2833:
2752:
2739:
2723:mismatch repair
2712:heterochromatin
2707:
2532:
2465:DNA methylation
2453:
2443:
1956:
1892:
1882:and hereditary
1804:
1799:
1793:
1723:
1688:naked mole-rats
1659:
1654:
1648:
1596:
1541:transcriptional
1515:gene expression
1507:
1365:
1210:
1154:
1111:point mutations
1074:DNA polymerases
1062:DNA replication
1058:
866:
849:Mismatch repair
802:excision repair
785:
722:
720:Direct reversal
698:
692:
666:
626:
564:and inside the
554:
465:creates mostly
447:bases creating
418:DNA replication
358:
350:gene conversion
252:
195:
185:
167:was awarded to
146:
37:
28:
23:
22:
15:
12:
11:
5:
10742:
10732:
10731:
10726:
10721:
10716:
10711:
10696:
10695:
10672:
10671:
10669:
10668:
10657:
10654:
10653:
10651:
10650:
10645:
10640:
10635:
10630:
10625:
10624:
10623:
10618:
10613:
10608:
10603:
10598:
10593:
10588:
10573:
10572:
10567:
10557:
10556:
10551:
10546:
10541:
10536:
10531:
10525:
10523:
10519:
10518:
10516:
10515:
10510:
10504:
10502:
10498:
10497:
10495:
10494:
10493:
10492:
10487:
10477:
10472:
10467:
10466:
10465:
10455:
10450:
10449:
10448:
10443:
10432:
10430:
10429:Other pathways
10426:
10425:
10423:
10422:
10417:
10412:
10407:
10402:
10401:
10400:
10390:
10385:
10379:
10377:
10371:
10370:
10368:
10367:
10366:
10365:
10360:
10350:
10349:
10348:
10343:
10338:
10333:
10328:
10323:
10318:
10313:
10308:
10303:
10298:
10293:
10279:
10278:
10277:
10272:
10267:
10252:
10250:
10244:
10243:
10236:
10235:
10228:
10221:
10213:
10207:
10206:
10153:
10125:(4): 589–605.
10110:
10105:
10100:
10088:
10083:
10071:(4): 755–762.
10065:Braz. J. Genet
10056:
10051:
10046:
10041:
10017:
10003:
9996:
9984:
9971:
9970:
9966:
9965:
9960:
9955:
9949:
9948:
9937:
9936:
9934:
9933:External links
9931:
9928:
9927:
9915:
9874:
9839:
9818:(6): 1163–74.
9812:Molecular Cell
9798:
9749:
9698:
9641:
9592:
9538:
9499:(25): 8905–9.
9479:
9425:
9376:
9327:
9278:
9243:
9184:
9133:
9084:
9044:
8995:
8943:
8894:
8845:
8794:
8765:(3): 590–600.
8745:
8716:(4): 1228–34.
8693:
8636:
8585:
8534:
8493:
8464:(4): 1151–62.
8444:
8411:Cancer Letters
8394:
8373:(5): 1268–74.
8353:
8312:
8269:
8220:
8179:
8130:
8105:
8079:
8067:
8016:
7957:
7936:(5): 1160–71.
7916:
7889:(5): 3851–57.
7872:
7851:(8): 2265–72.
7831:
7804:(7): 1017–26.
7787:
7736:
7695:
7666:(6): 797–802.
7646:
7603:
7554:
7503:
7447:
7426:(2): 196–227.
7406:
7357:
7322:Carcinogenesis
7308:
7269:(7): 3122–27.
7249:
7198:
7146:
7105:
7076:(7): 2225–38.
7056:
7007:
6961:
6910:
6853:
6826:Carcinogenesis
6809:
6758:
6707:
6653:
6602:
6549:
6514:
6463:
6414:
6363:
6352:
6330:
6306:
6263:
6214:
6195:(3): 295–307.
6178:
6127:
6076:
6047:(12): 952–65.
6027:
5984:
5957:
5942:
5915:(1–2): 22–35.
5898:
5841:
5792:
5757:
5722:
5678:
5657:(3): 599–610.
5637:
5606:
5599:
5577:
5570:
5552:
5501:
5458:
5406:
5362:
5313:
5284:(5): 887–900.
5264:
5218:
5174:
5122:
5093:(24): 3791–9.
5068:
5039:(14): 2233–7.
5019:
4970:
4956:
4921:
4895:
4866:(12): 2330–8.
4846:
4817:(31): 8070–9.
4797:
4748:
4720:
4669:
4618:
4569:
4530:(19): 7720–5.
4507:
4478:(2): 299–311.
4458:
4367:
4318:
4277:
4228:
4199:(5): 2164–73.
4179:
4122:
4078:
4035:
4012:
4005:
3987:
3972:
3939:
3932:
3914:
3907:
3884:
3833:
3805:
3776:(5): 1143–53.
3756:
3737:(6): 2203–37.
3721:
3684:10.1.1.318.738
3677:(3): 199–208.
3649:
3606:
3571:
3530:
3481:
3440:
3433:
3415:
3380:
3349:
3321:
3292:(11): 851–60.
3276:
3261:
3240:
3211:
3210:
3208:
3205:
3203:
3202:
3190:
3185:
3180:
3175:
3170:
3168:Life extension
3165:
3160:
3155:
3150:
3145:
3140:
3135:
3130:
3125:
3120:
3115:
3109:
3108:
3107:
3104:Biology portal
3091:
3088:
3079:
3076:
3054:
3051:
3035:photosynthetic
2998:bacteriophages
2981:
2978:
2970:
2967:
2945:
2942:
2891:
2887:
2883:
2879:
2875:
2871:
2847:
2843:
2835:
2831:
2776:Initiation of
2751:
2748:
2738:
2735:
2706:
2703:
2691:epigenetically
2604:carcinogenesis
2531:
2528:
2489:cell divisions
2452:
2449:
2440:
2439:
2432:
2430:
2428:
2426:
2419:
2417:
2410:
2406:
2405:
2403:
2396:
2394:
2387:
2380:
2378:
2371:
2367:
2366:
2364:
2362:
2355:
2353:
2351:
2344:
2342:
2336:
2335:
2328:
2321:
2314:
2312:
2310:
2308:
2306:
2302:
2301:
2299:
2292:
2285:
2283:
2281:
2279:
2277:
2273:
2272:
2270:
2263:
2256:
2254:
2252:
2250:
2243:
2239:
2238:
2236:
2234:
2232:
2225:
2223:
2221:
2214:
2210:
2209:
2207:
2205:
2203:
2196:
2194:
2192:
2185:
2179:
2178:
2176:
2174:
2172:
2165:
2163:
2161:
2154:
2148:
2147:
2145:
2138:
2136:
2134:
2127:
2125:
2118:
2114:
2113:
2111:
2109:
2107:
2105:
2103:
2096:
2089:
2085:
2084:
2082:
2080:
2078:
2076:
2069:
2062:
2055:
2051:
2050:
2048:
2046:
2044:
2042:
2035:
2028:
2021:
2017:
2016:
2013:
2010:
2007:
2004:
2001:
1998:
1995:
1955:
1952:
1891:
1888:
1876:Fanconi anemia
1861:
1860:
1854:
1840:
1827:
1826:
1820:
1814:
1803:
1800:
1795:Main article:
1792:
1789:
1783:theory of the
1744:metabolic rate
1722:
1719:
1658:
1655:
1650:Main article:
1647:
1644:
1619:may be in the
1616:shock response
1595:
1592:
1571:ATP hydrolysis
1546:that binds to
1506:
1503:
1461:protein kinase
1364:
1361:
1228:complexes and
1209:
1206:
1153:
1150:
1099:T^T photodimer
1091:UV irradiation
1066:thymine dimers
1057:
1054:
1042:Topoisomerases
992:
991:
971:
944:
865:
862:
861:
860:
846:
828:
784:
781:
768:stoichiometric
721:
718:
694:Main article:
691:
688:
665:
662:
642:Hayflick limit
625:
622:
553:
550:
546:ring puckering
542:
541:
526:vinyl chloride
519:
489:
474:
458:
428:
427:
424:
421:
411:
405:
389:
370:
357:
354:
341:
340:
339:
338:
333:
319:
310:
304:
294:
277:
276:
275:
271:also includes
251:
248:
184:
181:
137:
136:
126:
116:
26:
9:
6:
4:
3:
2:
10741:
10730:
10727:
10725:
10722:
10720:
10717:
10715:
10712:
10710:
10707:
10706:
10704:
10694:
10689:
10684:
10683:
10680:
10667:
10659:
10658:
10655:
10649:
10646:
10644:
10641:
10639:
10636:
10634:
10631:
10629:
10626:
10622:
10619:
10617:
10614:
10612:
10609:
10607:
10604:
10602:
10599:
10597:
10594:
10592:
10589:
10587:
10584:
10583:
10582:
10578:
10577:FANC proteins
10575:
10574:
10571:
10568:
10566:
10562:
10559:
10558:
10555:
10552:
10550:
10547:
10545:
10542:
10540:
10537:
10535:
10532:
10530:
10527:
10526:
10524:
10520:
10514:
10511:
10509:
10506:
10505:
10503:
10499:
10491:
10488:
10486:
10483:
10482:
10481:
10478:
10476:
10473:
10471:
10468:
10464:
10461:
10460:
10459:
10456:
10454:
10451:
10447:
10444:
10442:
10439:
10438:
10437:
10434:
10433:
10431:
10427:
10421:
10418:
10416:
10413:
10411:
10408:
10406:
10403:
10399:
10398:RecQ helicase
10396:
10395:
10394:
10391:
10389:
10386:
10384:
10381:
10380:
10378:
10376:
10372:
10364:
10361:
10359:
10356:
10355:
10354:
10351:
10347:
10344:
10342:
10339:
10337:
10334:
10332:
10329:
10327:
10324:
10322:
10319:
10317:
10314:
10312:
10309:
10307:
10304:
10302:
10299:
10297:
10294:
10292:
10289:
10288:
10287:
10283:
10280:
10276:
10273:
10271:
10268:
10266:
10263:
10262:
10261:
10257:
10254:
10253:
10251:
10249:
10245:
10241:
10234:
10229:
10227:
10222:
10220:
10215:
10214:
10211:
10203:
10199:
10194:
10189:
10184:
10179:
10175:
10171:
10167:
10163:
10159:
10154:
10150:
10146:
10141:
10136:
10132:
10128:
10124:
10120:
10116:
10111:
10109:
10106:
10104:
10101:
10099:
10095:
10092:
10089:
10087:
10084:
10079:
10074:
10070:
10066:
10062:
10057:
10055:
10052:
10050:
10047:
10045:
10042:
10039:
10034:
10030:
10029:
10025:
10021:
10006:
9964:
9961:
9959:
9956:
9954:
9951:
9950:
9945:
9940:
9924:
9919:
9911:
9907:
9902:
9897:
9893:
9889:
9885:
9878:
9870:
9866:
9862:
9858:
9855:(2): 720–52.
9854:
9850:
9843:
9835:
9831:
9826:
9821:
9817:
9813:
9809:
9802:
9794:
9790:
9785:
9780:
9776:
9772:
9768:
9764:
9760:
9753:
9745:
9741:
9736:
9731:
9726:
9721:
9717:
9713:
9709:
9702:
9694:
9690:
9685:
9680:
9676:
9672:
9668:
9664:
9660:
9656:
9652:
9645:
9637:
9633:
9628:
9623:
9619:
9615:
9612:(1): 126–40.
9611:
9607:
9606:Hum Mol Genet
9603:
9596:
9588:
9584:
9579:
9574:
9569:
9564:
9560:
9556:
9552:
9545:
9543:
9534:
9530:
9525:
9520:
9515:
9510:
9506:
9502:
9498:
9494:
9490:
9483:
9475:
9471:
9466:
9461:
9456:
9451:
9447:
9443:
9439:
9432:
9430:
9421:
9417:
9412:
9407:
9403:
9399:
9396:(3): 244–54.
9395:
9391:
9387:
9380:
9372:
9368:
9363:
9358:
9354:
9350:
9346:
9342:
9338:
9331:
9323:
9319:
9314:
9309:
9305:
9301:
9297:
9293:
9289:
9282:
9274:
9270:
9266:
9262:
9258:
9254:
9247:
9239:
9235:
9230:
9225:
9220:
9215:
9211:
9207:
9203:
9199:
9195:
9188:
9180:
9176:
9171:
9166:
9161:
9156:
9152:
9148:
9147:Int J Mol Sci
9144:
9137:
9129:
9125:
9120:
9115:
9111:
9107:
9103:
9099:
9095:
9088:
9080:
9076:
9072:
9068:
9064:
9060:
9053:
9051:
9049:
9040:
9036:
9031:
9026:
9022:
9018:
9014:
9010:
9009:J Am Chem Soc
9006:
8999:
8991:
8987:
8982:
8977:
8973:
8969:
8965:
8961:
8957:
8950:
8948:
8939:
8935:
8930:
8925:
8921:
8917:
8913:
8909:
8905:
8898:
8890:
8886:
8881:
8876:
8872:
8868:
8864:
8860:
8856:
8849:
8841:
8837:
8832:
8827:
8822:
8817:
8813:
8809:
8805:
8798:
8790:
8786:
8781:
8776:
8772:
8768:
8764:
8760:
8756:
8749:
8741:
8737:
8732:
8727:
8723:
8719:
8715:
8711:
8707:
8700:
8698:
8689:
8685:
8680:
8675:
8671:
8667:
8663:
8659:
8655:
8651:
8647:
8640:
8632:
8628:
8623:
8618:
8613:
8608:
8604:
8600:
8596:
8589:
8581:
8577:
8572:
8567:
8562:
8557:
8553:
8549:
8545:
8538:
8530:
8526:
8521:
8516:
8512:
8508:
8504:
8497:
8489:
8485:
8480:
8475:
8471:
8467:
8463:
8459:
8455:
8448:
8440:
8436:
8432:
8428:
8424:
8420:
8417:(1): 111–20.
8416:
8412:
8405:
8398:
8390:
8386:
8381:
8376:
8372:
8368:
8364:
8357:
8349:
8345:
8340:
8335:
8331:
8327:
8323:
8316:
8308:
8304:
8300:
8296:
8292:
8288:
8285:(2): 445–51.
8284:
8280:
8273:
8265:
8261:
8256:
8251:
8247:
8243:
8239:
8235:
8231:
8224:
8216:
8212:
8207:
8202:
8198:
8194:
8190:
8183:
8175:
8171:
8166:
8161:
8157:
8153:
8150:(2): 230–42.
8149:
8145:
8141:
8134:
8126:
8122:
8117:
8112:
8108:
8102:
8098:
8094:
8090:
8083:
8076:
8071:
8063:
8059:
8054:
8049:
8044:
8039:
8035:
8031:
8027:
8020:
8012:
8008:
8003:
7998:
7993:
7988:
7984:
7980:
7976:
7972:
7968:
7961:
7953:
7949:
7944:
7939:
7935:
7931:
7927:
7920:
7912:
7908:
7904:
7900:
7896:
7892:
7888:
7884:
7876:
7868:
7864:
7859:
7854:
7850:
7846:
7842:
7835:
7827:
7823:
7819:
7815:
7811:
7807:
7803:
7799:
7791:
7783:
7779:
7774:
7769:
7764:
7759:
7755:
7751:
7747:
7740:
7732:
7728:
7723:
7718:
7714:
7710:
7706:
7699:
7691:
7687:
7682:
7677:
7673:
7669:
7665:
7661:
7657:
7650:
7642:
7638:
7634:
7630:
7626:
7622:
7618:
7614:
7607:
7599:
7595:
7590:
7585:
7581:
7577:
7574:(4): 475–84.
7573:
7569:
7565:
7558:
7550:
7546:
7541:
7536:
7531:
7526:
7522:
7518:
7517:PLOS Genetics
7514:
7507:
7499:
7495:
7490:
7485:
7480:
7475:
7471:
7467:
7466:PLOS Genetics
7463:
7456:
7454:
7452:
7443:
7439:
7434:
7429:
7425:
7421:
7417:
7410:
7402:
7398:
7393:
7388:
7384:
7380:
7377:(3): 255–60.
7376:
7372:
7368:
7361:
7353:
7349:
7344:
7339:
7335:
7331:
7327:
7323:
7319:
7312:
7304:
7300:
7295:
7290:
7285:
7280:
7276:
7272:
7268:
7264:
7260:
7253:
7245:
7241:
7236:
7231:
7226:
7221:
7217:
7213:
7209:
7202:
7196:
7191:
7187:
7182:
7177:
7173:
7169:
7165:
7161:
7157:
7150:
7142:
7138:
7133:
7128:
7125:(4): 247–53.
7124:
7120:
7116:
7109:
7101:
7097:
7092:
7087:
7083:
7079:
7075:
7071:
7067:
7060:
7052:
7048:
7043:
7038:
7034:
7030:
7027:(4): 303–11.
7026:
7022:
7018:
7011:
7003:
6999:
6995:
6991:
6987:
6983:
6980:(2): 107–16.
6979:
6975:
6971:
6965:
6957:
6953:
6948:
6943:
6938:
6933:
6929:
6925:
6921:
6914:
6906:
6902:
6897:
6892:
6888:
6884:
6880:
6876:
6873:(2): 111–30.
6872:
6868:
6864:
6857:
6849:
6845:
6840:
6835:
6832:(3): 453–60.
6831:
6827:
6820:
6813:
6805:
6801:
6797:
6793:
6789:
6785:
6781:
6777:
6773:
6769:
6762:
6754:
6750:
6746:
6742:
6738:
6734:
6730:
6726:
6723:(5): 276–89.
6722:
6718:
6711:
6703:
6699:
6695:
6691:
6687:
6683:
6679:
6675:
6671:
6667:
6660:
6658:
6649:
6645:
6641:
6637:
6633:
6629:
6625:
6621:
6617:
6613:
6606:
6598:
6594:
6590:
6586:
6582:
6578:
6574:
6570:
6563:
6556:
6554:
6545:
6541:
6537:
6533:
6529:
6525:
6518:
6510:
6506:
6502:
6498:
6494:
6490:
6486:
6482:
6478:
6474:
6467:
6459:
6455:
6450:
6445:
6441:
6437:
6433:
6429:
6425:
6418:
6410:
6406:
6401:
6396:
6391:
6386:
6382:
6378:
6374:
6367:
6360:
6355:
6349:
6345:
6341:
6334:
6327:
6323:
6322:
6317:
6310:
6302:
6298:
6294:
6290:
6286:
6282:
6278:
6274:
6267:
6259:
6255:
6251:
6247:
6242:
6237:
6234:(3): 595–97.
6233:
6229:
6228:FASEB Journal
6225:
6218:
6210:
6206:
6202:
6198:
6194:
6190:
6182:
6174:
6170:
6166:
6162:
6158:
6154:
6150:
6146:
6142:
6138:
6131:
6123:
6119:
6115:
6111:
6107:
6103:
6099:
6095:
6091:
6087:
6080:
6072:
6068:
6063:
6058:
6054:
6050:
6046:
6042:
6038:
6031:
6023:
6019:
6015:
6011:
6007:
6003:
6000:(9): 960–66.
5999:
5995:
5988:
5980:
5976:
5973:(3): 134–35.
5972:
5968:
5961:
5951:
5949:
5947:
5938:
5934:
5930:
5926:
5922:
5918:
5914:
5910:
5902:
5894:
5890:
5886:
5882:
5877:
5872:
5868:
5864:
5860:
5856:
5852:
5845:
5837:
5833:
5828:
5823:
5819:
5815:
5812:(5): 503–09.
5811:
5807:
5803:
5796:
5788:
5784:
5780:
5776:
5772:
5768:
5761:
5753:
5749:
5745:
5741:
5738:(2): 406–19.
5737:
5733:
5726:
5718:
5714:
5709:
5704:
5701:(6): 637–56.
5700:
5696:
5692:
5685:
5683:
5674:
5670:
5665:
5660:
5656:
5652:
5648:
5641:
5633:
5629:
5626:(8): 639–49.
5625:
5621:
5617:
5610:
5602:
5596:
5591:
5590:
5581:
5573:
5567:
5563:
5556:
5548:
5544:
5540:
5536:
5532:
5528:
5524:
5520:
5516:
5512:
5505:
5497:
5493:
5489:
5485:
5481:
5477:
5473:
5469:
5462:
5454:
5450:
5445:
5440:
5436:
5432:
5429:(2): 235–49.
5428:
5424:
5420:
5413:
5411:
5402:
5398:
5393:
5388:
5384:
5380:
5376:
5369:
5367:
5358:
5354:
5349:
5344:
5340:
5336:
5332:
5328:
5324:
5317:
5309:
5305:
5301:
5297:
5292:
5287:
5283:
5279:
5275:
5268:
5260:
5256:
5251:
5246:
5242:
5238:
5234:
5227:
5225:
5223:
5214:
5210:
5205:
5200:
5196:
5192:
5188:
5181:
5179:
5170:
5166:
5161:
5156:
5152:
5148:
5144:
5140:
5136:
5129:
5127:
5118:
5114:
5109:
5104:
5100:
5096:
5092:
5088:
5084:
5077:
5075:
5073:
5064:
5060:
5055:
5050:
5046:
5042:
5038:
5034:
5030:
5023:
5015:
5011:
5006:
5001:
4997:
4993:
4990:(7): 533–47.
4989:
4985:
4981:
4974:
4965:
4963:
4961:
4952:
4948:
4944:
4940:
4936:
4932:
4925:
4909:
4905:
4899:
4891:
4887:
4882:
4877:
4873:
4869:
4865:
4861:
4857:
4850:
4842:
4838:
4833:
4828:
4824:
4820:
4816:
4812:
4808:
4801:
4793:
4789:
4784:
4779:
4775:
4771:
4768:(1): 134–54.
4767:
4763:
4759:
4752:
4745:
4741:
4735:
4731:
4724:
4716:
4712:
4708:
4704:
4700:
4696:
4692:
4688:
4684:
4680:
4673:
4665:
4661:
4656:
4651:
4646:
4641:
4637:
4633:
4629:
4622:
4614:
4610:
4605:
4600:
4596:
4592:
4588:
4584:
4580:
4573:
4565:
4561:
4556:
4551:
4546:
4541:
4537:
4533:
4529:
4525:
4521:
4514:
4512:
4503:
4499:
4495:
4491:
4486:
4481:
4477:
4473:
4469:
4462:
4450:
4442:
4435:
4431:
4427:
4423:
4419:
4412:
4408:
4403:
4398:
4394:
4390:
4386:
4382:
4378:
4371:
4363:
4359:
4354:
4349:
4345:
4341:
4338:(4): 849–60.
4337:
4333:
4329:
4322:
4314:
4310:
4305:
4300:
4296:
4292:
4288:
4281:
4273:
4269:
4264:
4259:
4255:
4251:
4247:
4243:
4239:
4232:
4224:
4220:
4215:
4210:
4206:
4202:
4198:
4194:
4190:
4183:
4175:
4171:
4167:
4163:
4158:
4157:10.1038/41365
4153:
4149:
4145:
4141:
4137:
4133:
4126:
4118:
4114:
4109:
4104:
4100:
4096:
4092:
4085:
4083:
4074:
4070:
4066:
4062:
4058:
4054:
4051:(7): 561–74.
4050:
4046:
4039:
4031:
4027:
4024:(1): 254–60.
4023:
4016:
4008:
4002:
3998:
3991:
3983:
3979:
3975:
3969:
3965:
3961:
3957:
3950:
3948:
3946:
3944:
3935:
3929:
3925:
3918:
3910:
3904:
3900:
3893:
3891:
3889:
3880:
3876:
3872:
3868:
3864:
3860:
3856:
3852:
3849:(2): 241–55.
3848:
3844:
3837:
3829:
3825:
3821:
3814:
3812:
3810:
3801:
3797:
3792:
3787:
3783:
3779:
3775:
3771:
3767:
3760:
3752:
3748:
3744:
3740:
3736:
3732:
3725:
3706:
3702:
3698:
3694:
3690:
3685:
3680:
3676:
3672:
3665:
3658:
3656:
3654:
3645:
3641:
3637:
3633:
3629:
3625:
3622:(9): 729–40.
3621:
3617:
3610:
3602:
3598:
3594:
3590:
3586:
3582:
3575:
3567:
3563:
3558:
3553:
3550:(6): 2881–4.
3549:
3545:
3541:
3534:
3526:
3522:
3517:
3512:
3508:
3504:
3500:
3496:
3492:
3485:
3476:
3471:
3467:
3463:
3459:
3455:
3451:
3444:
3436:
3430:
3426:
3419:
3411:
3407:
3403:
3399:
3395:
3391:
3384:
3369:
3368:
3360:
3353:
3338:
3337:
3332:
3325:
3317:
3313:
3309:
3305:
3300:
3295:
3291:
3287:
3280:
3272:
3268:
3264:
3258:
3254:
3247:
3245:
3229:. 5 July 2017
3228:
3227:
3222:
3216:
3212:
3201:
3200:
3195:
3191:
3189:
3186:
3184:
3181:
3179:
3176:
3174:
3171:
3169:
3166:
3164:
3161:
3159:
3156:
3154:
3151:
3149:
3146:
3144:
3141:
3139:
3136:
3134:
3131:
3129:
3126:
3124:
3121:
3119:
3116:
3114:
3111:
3110:
3105:
3099:
3094:
3087:
3085:
3075:
3072:
3068:
3064:
3060:
3050:
3048:
3044:
3040:
3039:free radicals
3036:
3032:
3027:
3026:Nucleic acids
3023:
3019:
3018:fossil record
3014:
3011:
3007:
3004:which infect
3003:
2999:
2995:
2991:
2987:
2977:
2975:
2966:
2962:
2959:
2955:
2951:
2941:
2938:
2934:
2933:messenger RNA
2929:
2925:
2921:
2917:
2913:
2909:
2905:
2901:
2900:HEK 293 cells
2896:
2868:
2866:
2862:
2859:
2855:
2854:
2841:
2828:
2826:
2822:
2817:
2815:
2807:
2803:
2799:
2795:
2791:
2787:
2783:
2779:
2774:
2770:
2768:
2764:
2761:
2757:
2747:
2745:
2734:
2732:
2728:
2724:
2720:
2717:
2713:
2702:
2700:
2696:
2692:
2688:
2684:
2679:
2675:
2670:
2668:
2664:
2660:
2656:
2652:
2648:
2644:
2640:
2636:
2632:
2628:
2624:
2620:
2619:
2614:
2613:
2607:
2605:
2601:
2597:
2591:
2587:
2583:
2581:
2577:
2572:
2570:
2566:
2562:
2558:
2553:
2551:
2547:
2536:
2527:
2525:
2521:
2516:
2512:
2510:
2506:
2500:
2498:
2492:
2490:
2486:
2482:
2478:
2474:
2470:
2466:
2461:
2459:
2431:
2429:
2427:
2418:
2408:
2407:
2404:
2395:
2379:
2369:
2368:
2365:
2363:
2354:
2352:
2343:
2341:
2338:
2337:
2313:
2311:
2309:
2307:
2304:
2303:
2300:
2284:
2282:
2280:
2278:
2275:
2274:
2271:
2255:
2253:
2251:
2241:
2240:
2237:
2235:
2233:
2224:
2222:
2212:
2211:
2208:
2206:
2204:
2195:
2193:
2184:
2181:
2180:
2177:
2175:
2173:
2164:
2162:
2153:
2150:
2149:
2146:
2137:
2135:
2126:
2116:
2115:
2112:
2110:
2108:
2106:
2104:
2087:
2086:
2083:
2081:
2079:
2077:
2053:
2052:
2049:
2047:
2045:
2043:
2019:
2018:
2014:
2011:
2008:
2005:
2002:
1999:
1996:
1994:
1993:
1990:
1987:
1981:
1979:
1975:
1971:
1965:
1962:
1951:
1947:
1944:
1940:
1936:
1932:
1927:
1924:
1920:
1915:
1913:
1912:
1907:
1906:
1901:
1897:
1887:
1885:
1881:
1880:breast cancer
1878:, hereditary
1877:
1872:
1870:
1866:
1858:
1855:
1852:
1848:
1844:
1841:
1838:
1835:
1834:
1833:
1830:
1824:
1821:
1818:
1815:
1812:
1809:
1808:
1807:
1798:
1788:
1786:
1782:
1777:
1772:
1770:
1769:
1764:
1759:
1757:
1753:
1749:
1745:
1741:
1737:
1727:
1718:
1716:
1715:radioactivity
1712:
1711:
1706:
1700:
1698:
1693:
1689:
1685:
1681:
1676:
1673:
1663:
1653:
1643:
1641:
1637:
1633:
1628:
1626:
1622:
1621:heterogeneity
1617:
1613:
1612:
1608:
1604:
1600:
1591:
1588:
1584:
1579:
1576:
1572:
1568:
1564:
1560:
1555:
1554:
1549:
1545:
1542:
1538:
1534:
1530:
1526:
1522:
1521:
1516:
1512:
1502:
1500:
1496:
1492:
1489:
1485:
1481:
1476:
1474:
1470:
1466:
1462:
1458:
1453:
1451:
1447:
1443:
1439:
1435:
1431:
1429:
1425:
1421:
1417:
1413:
1412:phosphorylate
1409:
1405:
1401:
1397:
1393:
1389:
1385:
1381:
1377:
1373:
1370:
1360:
1358:
1354:
1350:
1346:
1342:
1339:
1335:
1330:
1328:
1324:
1320:
1316:
1312:
1308:
1304:
1300:
1296:
1292:
1290:
1286:
1282:
1277:
1273:
1268:
1266:
1261:
1257:
1254:
1250:
1246:
1242:
1238:
1233:
1231:
1227:
1223:
1219:
1215:
1208:Initial steps
1205:
1203:
1202:cell division
1199:
1195:
1191:
1187:
1183:
1179:
1175:
1174:carbohydrates
1171:
1167:
1163:
1159:
1149:
1147:
1142:
1139:
1135:
1131:
1126:
1122:
1117:
1112:
1108:
1104:
1100:
1096:
1092:
1088:
1084:
1080:
1075:
1071:
1067:
1063:
1053:
1049:
1047:
1043:
1039:
1037:
1033:
1029:
1025:
1021:
1017:
1013:
1009:
1008:
1004:
999:
997:
989:
985:
981:
977:
972:
969:
965:
961:
957:
953:
949:
948:end resection
945:
942:
941:immune system
939:
935:
931:
927:
923:
919:
915:
911:
910:DNA Ligase IV
907:
906:
902:
897:
893:
891:
887:
883:
879:
870:
858:
854:
850:
847:
844:
840:
839:endonucleases
836:
832:
829:
825:
822:
818:
814:
810:
807:
806:
805:
803:
794:
789:
780:
777:
773:
769:
765:
760:
756:
752:
748:
744:
740:
739:blue/UV light
736:
732:
728:
717:
713:
711:
707:
703:
697:
687:
683:
679:
675:
672:
661:
659:
655:
651:
647:
643:
639:
638:noncoding DNA
635:
631:
621:
619:
615:
611:
607:
603:
599:
598:free radicals
595:
591:
587:
583:
582:cell division
579:
575:
571:
567:
563:
559:
549:
547:
539:
535:
531:
527:
523:
520:
517:
513:
509:
505:
501:
497:
493:
490:
486:
485:
480:
479:
475:
472:
468:
467:free radicals
464:
463:
459:
456:
452:
451:
446:
442:
438:
437:
433:
432:
431:
425:
422:
419:
415:
412:
409:
406:
403:
399:
395:
394:
390:
388:
384:
380:
376:
375:
371:
368:
367:
363:
362:
361:
353:
351:
347:
346:back mutation
337:
334:
332:
328:
325:, especially
324:
320:
318:
315:
311:
308:
305:
303:
299:
295:
292:
288:
284:
281:
280:
278:
274:
270:
269:
268:
264:
260:
257:
256:
255:
247:
245:
241:
237:
233:
229:
225:
220:
215:
213:
209:
205:
200:
194:
190:
180:
178:
174:
170:
169:Tomas Lindahl
166:
144:
142:
135:
131:
127:
125:
121:
117:
115:
111:
110:
109:
105:
103:
99:
95:
91:
87:
83:
79:
75:
71:
67:
63:
59:
55:
51:
43:
39:
35:
30:
19:
10580:
10561:DNA helicase
10544:8-Oxoguanine
10513:SOS response
10393:RecF pathway
10346:Excinuclease
10239:
10165:
10161:
10122:
10118:
10068:
10064:
9953:Online books
9943:
9918:
9894:(1): 38–46.
9891:
9887:
9877:
9852:
9848:
9842:
9815:
9811:
9801:
9766:
9762:
9752:
9715:
9712:BMC Genomics
9711:
9701:
9658:
9654:
9644:
9609:
9605:
9595:
9558:
9554:
9496:
9492:
9482:
9445:
9441:
9393:
9389:
9379:
9344:
9340:
9330:
9298:(1): 23–38.
9295:
9291:
9281:
9256:
9252:
9246:
9201:
9197:
9187:
9153:(21): 8360.
9150:
9146:
9136:
9101:
9097:
9087:
9062:
9058:
9012:
9008:
8998:
8963:
8959:
8911:
8907:
8897:
8865:(1): 71–75.
8862:
8858:
8848:
8811:
8807:
8797:
8762:
8758:
8748:
8713:
8710:Cell Reports
8709:
8653:
8649:
8639:
8602:
8598:
8588:
8551:
8547:
8537:
8510:
8506:
8496:
8461:
8457:
8447:
8414:
8410:
8397:
8370:
8366:
8356:
8329:
8325:
8315:
8282:
8278:
8272:
8237:
8233:
8223:
8196:
8192:
8182:
8147:
8143:
8133:
8088:
8082:
8070:
8033:
8029:
8019:
7974:
7970:
7960:
7933:
7929:
7919:
7886:
7882:
7875:
7848:
7844:
7834:
7801:
7797:
7790:
7753:
7749:
7739:
7712:
7708:
7698:
7663:
7659:
7649:
7616:
7612:
7606:
7571:
7567:
7557:
7520:
7516:
7506:
7469:
7465:
7423:
7419:
7409:
7374:
7371:EMBO Reports
7370:
7360:
7325:
7321:
7311:
7266:
7262:
7252:
7218:(3): 43–49.
7215:
7211:
7201:
7166:(1): 51–58.
7163:
7159:
7149:
7122:
7118:
7108:
7073:
7069:
7059:
7024:
7020:
7010:
6977:
6973:
6964:
6927:
6923:
6913:
6870:
6866:
6856:
6829:
6825:
6812:
6771:
6767:
6761:
6737:10261/123721
6720:
6716:
6710:
6669:
6665:
6615:
6611:
6605:
6575:(1): 35–42.
6572:
6568:
6527:
6523:
6517:
6476:
6472:
6466:
6431:
6427:
6417:
6380:
6376:
6366:
6357:
6343:
6333:
6325:
6319:
6309:
6276:
6272:
6266:
6231:
6227:
6217:
6192:
6188:
6181:
6140:
6136:
6130:
6089:
6085:
6079:
6044:
6040:
6030:
5997:
5993:
5987:
5970:
5966:
5960:
5912:
5908:
5901:
5858:
5854:
5844:
5809:
5806:EMBO Reports
5805:
5795:
5770:
5766:
5760:
5735:
5731:
5725:
5698:
5694:
5654:
5650:
5640:
5623:
5619:
5609:
5588:
5580:
5561:
5555:
5514:
5510:
5504:
5474:(1): 37–45.
5471:
5467:
5461:
5426:
5422:
5382:
5378:
5330:
5326:
5316:
5281:
5277:
5267:
5240:
5236:
5194:
5190:
5142:
5139:Cell Reports
5138:
5090:
5086:
5036:
5032:
5022:
4987:
4983:
4973:
4937:(2): 59–70.
4934:
4930:
4924:
4912:. Retrieved
4908:the original
4898:
4863:
4860:Biochemistry
4859:
4849:
4814:
4811:Biochemistry
4810:
4800:
4765:
4761:
4751:
4729:
4723:
4682:
4678:
4672:
4635:
4631:
4621:
4589:(3): e1697.
4586:
4582:
4572:
4527:
4523:
4475:
4471:
4461:
4447:{{
4439:{{
4384:
4380:
4370:
4335:
4331:
4321:
4294:
4290:
4280:
4245:
4241:
4231:
4196:
4192:
4182:
4139:
4135:
4125:
4098:
4094:
4048:
4044:
4038:
4021:
4015:
3996:
3990:
3955:
3923:
3917:
3898:
3846:
3842:
3836:
3819:
3773:
3769:
3759:
3734:
3730:
3724:
3714:29 September
3712:. Retrieved
3705:the original
3674:
3670:
3619:
3615:
3609:
3587:(2): 69–78.
3584:
3580:
3574:
3547:
3543:
3533:
3498:
3494:
3484:
3460:(2): 56–61.
3457:
3453:
3443:
3424:
3418:
3393:
3389:
3383:
3371:. Retrieved
3365:
3352:
3340:. Retrieved
3334:
3324:
3289:
3285:
3279:
3252:
3231:. Retrieved
3224:
3215:
3197:
3193:
3153:Gene therapy
3081:
3056:
3015:
2983:
2972:
2963:
2947:
2910:(K2CrO4)).
2897:
2869:
2864:
2857:
2852:
2829:
2823:it recruits
2818:
2811:
2753:
2740:
2708:
2677:
2671:
2666:
2662:
2654:
2650:
2646:
2642:
2638:
2634:
2616:
2610:
2608:
2599:
2592:
2588:
2584:
2573:
2554:
2542:
2517:
2513:
2501:
2493:
2485:DNA sequence
2462:
2454:
1982:
1966:
1957:
1948:
1933:) inhibitor
1928:
1923:radiotherapy
1919:chemotherapy
1916:
1909:
1903:
1893:
1884:colon cancer
1873:
1862:
1849:(especially
1847:malignancies
1831:
1828:
1805:
1775:
1773:
1766:
1760:
1732:
1708:
1701:
1677:
1668:
1629:
1609:
1597:
1582:
1580:
1567:DNA helicase
1551:
1518:
1511:SOS response
1508:
1477:
1459:(PI3K)-like
1454:
1440:that blocks
1433:
1432:
1366:
1332:After rapid
1331:
1293:
1269:
1234:
1211:
1166:biomolecules
1155:
1124:
1120:
1079:processivity
1059:
1050:
1046:supercoiling
1040:
1030:by means of
1005:
1003:extremophile
1000:
995:
993:
888:(MMEJ), and
875:
856:
853:proofreading
843:Uvr proteins
798:
770:rather than
723:
714:
699:
684:
680:
676:
667:
627:
566:mitochondria
555:
543:
521:
496:depurination
491:
482:
476:
460:
448:
434:
429:
413:
402:depurination
391:
372:
364:
359:
342:
253:
216:
196:
173:Paul Modrich
162:
138:
106:
49:
48:
38:
29:
9561:(7): e110.
9253:Cell Signal
9104:: 207–219.
9059:Cell Signal
8908:Toxicol Sci
8831:10230/35343
7523:(7): e110.
7119:Mutagenesis
4730:Radiat Res.
4420:, see
3396:: 577–628.
3367:Nobel Prize
3178:REPAIRtoire
3022:Precambrian
2990:prokaryotes
2988:among both
2906:(KBrO3) or
2788:), forming
1763:gene dosage
1640:polymerases
1587:palindromic
1559:Spirochetes
1535:. The LexA
1525:prokaryotic
1501:complexes.
1473:chromosomes
1372:checkpoints
1341:checkpoints
1116:polymerases
1034:-dependent
813:glycosylase
753:, and most
578:chromosomes
508:hot springs
484:cosmic rays
398:deamination
379:methylation
321:human-made
283:ultraviolet
240:supercoiled
177:Aziz Sancar
100:as per the
10729:Senescence
10709:DNA repair
10703:Categories
10501:Regulation
10480:Photolyase
10240:DNA repair
10091:DNA Repair
10038:DNA repair
10020:Audio help
10011:2005-06-17
9944:DNA repair
9763:Oncotarget
9718:(1): 856.
9555:PLOS Genet
9448:(1): 225.
8599:BMC Cancer
8554:: 946268.
6530:: 129–43.
6377:BMC Cancer
6189:DNA Repair
5773:: 357–77.
5033:Cell Cycle
3924:i Genetics
3495:Cell Cycle
3233:7 November
3207:References
3194:DNA Repair
3183:Senescence
3123:Cell cycle
3078:Technology
3033:") due to
2994:eukaryotes
2861:CpG island
2840:TET enzyme
2760:methylated
2678:inaccurate
1986:cell cycle
1781:pleiotropy
1776:C. elegans
1756:DNA damage
1599:Eukaryotic
1442:cell cycle
1369:cell cycle
1338:cell cycle
1224:dependent
1198:cell cycle
1093:, whereas
1020:homologous
938:vertebrate
922:eukaryotes
914:DNA ligase
743:wavelength
735:photolyase
690:Mechanisms
650:cell cycle
646:quiescence
604:(ATP) via
596:(ROS), or
590:organelles
574:cell cycle
558:eukaryotic
462:UV-A light
436:UV-B light
393:hydrolysis
374:alkylation
307:hydrolysis
302:gamma rays
259:endogenous
183:DNA damage
114:senescence
78:transcribe
50:DNA repair
10321:XPG/ERCC5
10306:XPD/ERCC2
9661:: 33222.
6970:Baylin SB
6930:(4): 14.
6434:: 65–83.
4914:14 August
3828:936762772
3679:CiteSeerX
3373:7 October
3342:7 October
3294:CiteSeerX
3118:Aging DNA
3071:evolution
3063:germ line
3059:mutations
2986:conserved
2980:Evolution
2958:CpG sites
2786:CpG sites
2481:microRNAs
1865:progerias
1851:leukemias
1697:longevity
1625:mammalian
1544:repressor
1537:homodimer
1484:apoptosis
1446:metaphase
1329:damages.
1315:PARylates
1309:and with
1253:polymeric
1218:remodeled
1214:chromatin
1190:apoptosis
1028:crossover
1016:annealing
980:chromatid
908:In NHEJ,
772:catalytic
706:chromatid
634:telomeres
618:cytoplasm
570:chromatin
498:(loss of
366:oxidation
289:(200–400
287:radiation
199:metabolic
163:The 2015
141:life span
134:cancerous
120:apoptosis
94:apoptosis
86:mutations
70:radiation
66:metabolic
10724:Mutation
10666:Category
10316:XPF/DDB1
10311:XPE/DDB1
10202:26966913
10162:PLOS ONE
10149:18285820
10094:Archived
10022: ·
9910:16437551
9869:16464022
9834:11779493
9793:28423717
9744:33267773
9693:27629060
9636:20940144
9587:17616978
9533:15956212
9474:31963223
9420:26186941
9371:24108092
9322:22781841
9273:27251462
9238:15365186
9179:33171795
9128:31993111
9079:27251462
9039:24571128
8990:11353081
8938:21163908
8889:24336318
8840:28753428
8789:23622243
8740:25456125
8688:25707793
8631:23442605
8580:23762867
8529:14562054
8507:Oncogene
8488:12651607
8439:44644467
8431:15922863
8389:24590400
8348:15701830
8307:22165252
8299:16879693
8264:19010819
8215:22286769
8193:Oncogene
8174:23249749
8125:22956494
8062:22494821
8036:(1): 3.
8011:20351277
7952:15887099
7911:18733871
7903:23271133
7867:23422094
7818:21706233
7782:20653064
7731:16174854
7690:15888787
7598:21779515
7549:17616978
7498:18704159
7401:11850397
7352:16728433
7244:23671730
7190:21278452
7141:17412712
7100:12640109
7051:22082348
6994:16491070
6956:15125777
6905:24397478
6848:10688865
6804:16426080
6796:18323444
6753:11342123
6745:25907220
6694:17136093
6640:15829956
6597:14941857
6589:26667849
6544:25423595
6501:15829966
6458:26896565
6409:17683622
6293:10830948
6258:43118901
6250:14734635
6209:12547392
6173:33503081
6165:15205477
6114:11242085
6071:23363784
6014:15927235
5979:15858357
5937:16472827
5893:41930529
5885:11950998
5836:15105825
5787:16153173
5752:16464012
5717:17883408
5673:11833768
5632:12479224
5539:12556884
5488:16327781
5453:23045548
5401:17635991
5357:22531782
5308:14232192
5300:18001824
5213:18025084
5169:27568560
5117:27733626
5063:19502789
5014:23633913
4951:11425512
4890:21302943
4841:18616294
4792:19258535
4744:12643795
4707:17006450
4664:23565119
4613:25789972
4564:23610439
4502:16890458
4494:14744439
4434:32239214
4411:12954774
4362:15692565
4313:10438542
4117:16012167
4073:33154242
3982:16793370
3879:24722637
3800:19228922
3751:12797829
3701:19594328
3644:15664931
3636:17667954
3601:16460230
3566:16540631
3525:16940754
3410:10547702
3316:15589490
3271:53798180
3173:Progeria
3090:See also
3006:bacteria
2937:promoter
2924:promoter
2821:CpG site
2782:CpG site
2763:CpG site
2727:H3K36me3
2719:H3K36me3
2689:site is
2600:accurate
2565:microRNA
1943:Olaparib
1935:olaparib
1672:lymphoma
1575:protease
1548:operator
1305:protein
1170:proteins
1168:such as
1141:proteins
1070:AP sites
996:in vitro
884:(NHEJ),
857:E. coli
747:bacteria
664:Mutation
610:toxicity
586:histones
524:such as
441:cytosine
414:mismatch
327:aromatic
312:certain
244:histones
228:proteins
132:that is
10693:Biology
10508:SOS box
10260:AP site
10193:4788447
10170:Bibcode
10140:2262034
10009: (
9980:minutes
9784:5522286
9735:7709351
9684:5024116
9663:Bibcode
9655:Sci Rep
9627:3000680
9578:1913100
9524:1157029
9501:Bibcode
9465:7016758
9411:4937888
9362:3858462
9313:3521964
9206:Bibcode
9170:7664663
9119:6974700
9030:3985951
8929:3043087
8880:4116484
8780:3641580
8731:4254608
8679:4425546
8658:Bibcode
8622:3599366
8571:3666359
8479:1851213
8255:2948671
8165:3543090
8116:3707278
8053:3351028
8002:2872463
7979:Bibcode
7826:8069716
7773:2909555
7681:1774551
7641:9353177
7621:Bibcode
7613:Science
7589:3135649
7540:1913100
7489:2491723
7442:5770175
7433:1706430
7392:1084010
7343:2612936
7303:9096356
7271:Bibcode
7235:3648662
7181:3030973
7042:3590802
7002:2514545
6896:4064942
6875:Bibcode
6776:Bibcode
6768:Science
6702:4406956
6674:Bibcode
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6620:Bibcode
6509:4391043
6481:Bibcode
6449:4811676
6400:1959234
6383:: 152.
6301:4402039
6145:Bibcode
6137:Science
6122:4356885
6094:Bibcode
6062:3615161
6022:7067036
5917:Bibcode
5863:Bibcode
5855:Science
5827:1299048
5547:4403303
5519:Bibcode
5496:9797133
5444:3471223
5348:3365417
5259:9488723
5160:5089070
5108:5170603
5054:3856216
5005:3468886
4881:3062377
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4687:Bibcode
4655:3613618
4604:4385936
4555:3651503
4532:Bibcode
4272:8890183
4223:8628283
4174:4422938
4166:9242411
4144:Bibcode
4065:5106728
4030:5055816
3871:3278898
3851:Bibcode
3791:2668831
3516:3488278
3462:Bibcode
3002:viruses
2800:enzyme
2569:miR-155
2497:genetic
2445:repair)
1396:kinases
1345:kinases
1276:histone
1125:E. coli
1081:factor
936:in the
827:ligase.
817:AP site
755:animals
630:divides
580:during
562:nucleus
488:cancer.
445:thymine
336:viruses
250:Sources
224:adducts
90:mitosis
10679:Portal
10633:FANCD2
10628:FANCD1
10388:RecBCD
10341:RAD23B
10336:RAD23A
10200:
10190:
10147:
10137:
10119:EMBO J
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3196:under
3084:CRISPR
3067:gamete
2507:or in
1890:Cancer
1692:humans
1495:cyclin
1426:, and
1180:, and
1178:lipids
1134:lesion
1101:using
1024:D-loop
994:In an
930:B-cell
892:(HR):
702:genome
658:cancer
512:purine
500:purine
317:toxins
298:x-rays
175:, and
98:cancer
62:genome
10648:FANCN
10643:FANCJ
10638:FANCI
10621:FANCM
10616:FANCL
10611:FANCG
10606:FANCF
10601:FANCE
10596:FANCC
10591:FANCB
10586:FANCA
10446:ERCC8
10441:ERCC6
10405:RAD51
10326:ERCC1
9442:Cells
8981:55450
8435:S2CID
8407:(PDF)
8303:S2CID
7907:S2CID
7822:S2CID
7294:20332
6998:S2CID
6822:(PDF)
6800:S2CID
6749:S2CID
6698:S2CID
6644:S2CID
6593:S2CID
6565:(PDF)
6505:S2CID
6297:S2CID
6254:S2CID
6169:S2CID
6118:S2CID
6041:Aging
6018:S2CID
5889:S2CID
5543:S2CID
5492:S2CID
5304:S2CID
4711:S2CID
4498:S2CID
4445:with
4170:S2CID
4069:S2CID
3875:S2CID
3708:(PDF)
3667:(PDF)
3640:S2CID
3362:(PDF)
3188:SiDNA
2928:BRCA1
2865:BACE1
2858:BACE1
2853:BACE1
2780:at a
2667:BRCA2
2663:RAD51
2655:BRCA2
2651:RAD51
2647:BRCA2
2643:RAD51
2639:BRCA2
2635:RAD51
2631:BRCA2
2627:RAD51
2618:BRCA2
2612:RAD51
2576:ERCC1
2477:HMGA1
2473:HMGA2
2370:ERCC1
2340:PARP1
2276:XRCC1
2213:RAD51
2183:BRCA2
2152:BRCA1
2088:PAXIP
1931:PARP1
1911:BRCA2
1905:BRCA1
1705:below
1646:Aging
1607:yeast
1539:is a
1436:is a
1428:53BP1
1420:BRCA1
1311:PARP1
1307:CUL4A
1265:MRE11
1249:PARP1
1241:SIRT6
1194:genes
1146:Pol ζ
1138:RAD18
1095:Pol ι
1087:Pol η
964:XRCC1
952:MRE11
918:XRCC4
901:ester
751:fungi
356:Types
314:plant
285:(UV)
208:tumor
130:tumor
10534:PcrA
10490:CRY2
10485:CRY1
10420:LexA
10415:Slx4
10410:Sgs1
10383:RecA
10363:MSH2
10358:MLH1
10286:ERCC
10198:PMID
10145:PMID
9906:PMID
9865:PMID
9830:PMID
9789:PMID
9740:PMID
9689:PMID
9632:PMID
9583:PMID
9529:PMID
9470:PMID
9416:PMID
9367:PMID
9318:PMID
9269:PMID
9234:PMID
9175:PMID
9124:PMID
9075:PMID
9035:PMID
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8934:PMID
8885:PMID
8836:PMID
8808:Cell
8785:PMID
8759:Cell
8736:PMID
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8627:PMID
8576:PMID
8552:2013
8525:PMID
8484:PMID
8427:PMID
8385:PMID
8344:PMID
8295:PMID
8260:PMID
8211:PMID
8170:PMID
8121:PMID
8101:ISBN
8058:PMID
8007:PMID
7948:PMID
7899:PMID
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7814:PMID
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6901:PMID
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6497:PMID
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6289:PMID
6246:PMID
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6110:PMID
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5933:PMID
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5278:Cell
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5010:PMID
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4916:2012
4886:PMID
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4430:PMID
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4268:PMID
4219:PMID
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4061:PMID
4026:PMID
4001:ISBN
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3928:ISBN
3903:ISBN
3867:PMID
3824:OCLC
3796:PMID
3747:PMID
3716:2009
3697:PMID
3632:PMID
3597:PMID
3562:PMID
3521:PMID
3429:ISBN
3406:PMID
3375:2015
3344:2015
3312:PMID
3267:OCLC
3257:ISBN
3235:2018
3016:The
2992:and
2825:TET1
2806:TET1
2802:OGG1
2699:MMEJ
2695:MMEJ
2683:FEN1
2637:and
2629:and
2615:and
2561:MLH1
2557:PMS2
2550:MGMT
2495:the
2409:MSH3
2305:PCNA
2015:MMR
2000:NHEJ
1921:and
1908:and
1867:" ("
1774:The
1748:mTOR
1690:and
1684:mice
1678:The
1533:RecA
1531:and
1529:LexA
1509:The
1424:MDC1
1402:and
1382:and
1357:Chk1
1351:and
1319:ALC1
1299:DDB1
1295:DDB2
1289:NuRD
1285:CHD4
1281:RNF8
1272:H2AX
1260:ALC1
1083:PCNA
1032:RecA
1001:The
968:LIG3
932:and
824:nick
528:and
443:and
300:and
230:and
191:and
82:gene
80:the
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10570:WRN
10565:BLM
10529:Ogt
10331:RPA
10301:XPC
10296:XPB
10291:XPA
10188:PMC
10178:doi
10135:PMC
10127:doi
10073:doi
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4868:doi
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4683:443
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2687:ETS
2665:or
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2645:or
2580:XPF
2475:or
2242:RFC
2117:RPA
2054:ATR
2020:ATM
2012:NER
2009:BER
2003:SSA
1974:ATM
1682:of
1623:of
1581:In
1517:in
1491:p21
1480:p53
1450:DNA
1404:ATR
1400:ATM
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1349:ATM
1222:ATP
1182:RNA
1128:by
1068:or
950:by
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122:or
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