DNA mismatch repair#MutL homologs

{{More citations needed section|date=May 2024}}

{{Infobox protein family

| Symbol = DNA_mis_repair

| Name = DNA mismatch repair protein, C-terminal domain

| image = PDB 1h7u EBI.jpg

| width =

| caption = hpms2-atpgs

| Pfam = PF01119

| Pfam_clan = CL0329

| InterPro = IPR013507

| SMART =

| PROSITE = PDOC00057

| MEROPS =

| SCOP = 1bkn

| TCDB =

| OPM family =

| OPM protein =

| CAZy =

| CDD =

}}

Mismatch repair is a highly conserved process from prokaryotes to eukaryotes. The first evidence for mismatch repair was obtained from S. pneumoniae (the hexA and hexB genes). Subsequent work on E. coli has identified a number of genes that, when mutationally inactivated, cause hypermutable strains. The gene products are, therefore, called the "Mut" proteins, and are the major active components of the mismatch repair system. Three of these proteins are essential in detecting the mismatch and directing repair machinery to it: MutS, MutH and MutL (MutS is a homologue of HexA and MutL of HexB).

MutS forms a dimer (MutS₂) that recognises the mismatched base on the daughter strand and binds the mutated DNA. MutH binds at hemimethylated sites along the daughter DNA, but its action is latent, being activated only upon contact by a MutL dimer (MutL₂), which binds the MutS-DNA complex and acts as a mediator between MutS₂ and MutH, activating the latter. The DNA is looped out to search for the nearest d(GATC) methylation site to the mismatch, which could be up to 1 kb away. Upon activation by the MutS-DNA complex, MutH nicks the daughter strand near the hemimethylated site. MutL recruits UvrD helicase (DNA Helicase II) to separate the two strands with a specific 3' to 5' polarity. The entire MutSHL complex then slides along the DNA in the direction of the mismatch, liberating the strand to be excised as it goes. An exonuclease trails the complex and digests the ss-DNA tail. The exonuclease recruited is dependent on which side of the mismatch MutH incises the strand – 5' or 3'. If the nick made by MutH is on the 5' end of the mismatch, either RecJ or ExoVII (both 5' to 3' exonucleases) is used. If, however, the nick is on the 3' end of the mismatch, ExoI (a 3' to 5' enzyme) is used.

The entire process ends past the mismatch site – i.e., both the site itself and its surrounding nucleotides are fully excised. The single-strand gap created by the exonuclease can then be repaired by DNA Polymerase III (assisted by single-strand-binding protein), which uses the other strand as a template, and finally sealed by DNA ligase. DNA methylase then rapidly methylates the daughter strand.

When bound, the MutS₂ dimer bends the DNA helix and shields approximately 20 base pairs. It has weak ATPase activity, and binding of ATP leads to the formation of tertiary structures on the surface of the molecule. The crystal structure of MutS reveals that it is exceptionally asymmetric, and, while its active conformation is a dimer, only one of the two halves interacts with the mismatch site.

In eukaryotes, MutS homologs form two major heterodimers: Msh2/Msh6 (MutSα) and Msh2/Msh3 (MutSβ). The MutSα pathway is involved primarily in base substitution and small-loop mismatch repair. The MutSβ pathway is also involved in small-loop repair, in addition to large-loop (~10 nucleotide loops) repair. However, MutSβ does not repair base substitutions.

MutL also has weak ATPase activity (it uses ATP for purposes of movement). It forms a complex with MutS and MutH, increasing the MutS footprint on the DNA.

However, the processivity (the distance the enzyme can move along the DNA before dissociating) of UvrD is only ~40–50 bp. Because the distance between the nick created by MutH and the mismatch can average ~600 bp, if there is not another UvrD loaded the unwound section is then free to re-anneal to its complementary strand, forcing the process to start over. However, when assisted by MutL, the rate of UvrD loading is greatly increased. While the processivity (and ATP utilisation) of the individual UvrD molecules remains the same, the total effect on the DNA is boosted considerably; the DNA has no chance to re-anneal, as each UvrD unwinds 40-50 bp of DNA, dissociates, and then is immediately replaced by another UvrD, repeating the process. This exposes large sections of DNA to exonuclease digestion, allowing for quick excision (and later replacement) of the incorrect DNA.

Eukaryotes have five MutL homologs designated as MLH1, MLH2, MLH3, PMS1, and PMS2. They form heterodimers that mimic MutL in E. coli. The human homologs of prokaryotic MutL form three complexes referred to as MutLα, MutLβ, and MutLγ. The MutLα complex is made of MLH1 and PMS2 subunits, the MutLβ heterodimer is made of MLH1 and PMS1, whereas MutLγ is made of MLH1 and MLH3. MutLα acts as an endonuclease that introduces strand breaks in the daughter strand upon activation by mismatch and other required proteins, MutSα and PCNA. These strand interruptions serve as entry points for an exonuclease activity that removes mismatched DNA. Roles played by MutLβ and MutLγ in mismatch repair are less-understood.

MutH is a very weak endonuclease that is activated once bound to MutL (which itself is bound to MutS). It nicks unmethylated DNA and the unmethylated strand of hemimethylated DNA but does not nick fully methylated DNA. Experiments have shown that mismatch repair is random if neither strand is methylated.{{citation needed|date=September 2017}} These behaviours led to the proposal that MutH determines which strand contains the mismatch.

MutH has no eukaryotic homolog. Its endonuclease function is taken up by MutL homologs, which have some specialized 5'-3' exonuclease activity. The strand bias for removing mismatches from the newly synthesized daughter strand in eukaryotes may be provided by the free 3' ends of Okazaki fragments in the new strand created during replication.

PCNA and the β-sliding clamp associate with MutSα/β and MutL, respectively. Although initial reports suggested that the PCNA-MutSα complex may enhance mismatch recognition,{{cite journal | vauthors = Flores-Rozas H, Clark D, Kolodner RD | title = Proliferating cell nuclear antigen and Msh2p-Msh6p interact to form an active mispair recognition complex | journal = Nature Genetics | volume = 26 | issue = 3 | pages = 375–8 | date = November 2000 | pmid = 11062484 | doi = 10.1038/81708 | s2cid = 20861705 }} it has been recently demonstrated{{cite journal | vauthors = Iyer RR, Pohlhaus TJ, Chen S, Hura GL, Dzantiev L, Beese LS, Modrich P | title = The MutSalpha-proliferating cell nuclear antigen interaction in human DNA mismatch repair | journal = The Journal of Biological Chemistry | volume = 283 | issue = 19 | pages = 13310–9 | date = May 2008 | pmid = 18326858 | pmc = 2423938 | doi = 10.1074/jbc.M800606200 | doi-access = free }} that there is no apparent change in affinity of MutSα for a mismatch in the presence or absence of PCNA. Furthermore, mutants of MutSα that are unable to interact with PCNA in vitro exhibit the capacity to carry out mismatch recognition and mismatch excision to near wild type levels. Such mutants are defective in the repair reaction directed by a 5' strand break, suggesting for the first time MutSα function in a post-excision step of the reaction.

Mutations in the human homologues of the Mut proteins affect genomic stability, which can result in microsatellite instability (MSI), implicated in some human cancers. In specific, the hereditary nonpolyposis colorectal cancers (HNPCC or Lynch syndrome) are attributed to damaging germline variants in the genes encoding the MutS and MutL homologues MSH2 and MLH1 respectively, which are thus classified as tumour suppressor genes. One subtype of HNPCC, the Muir-Torre Syndrome (MTS), is associated with skin tumors. If both inherited copies (alleles) of a MMR gene bear damaging genetic variants, this results in a very rare and severe condition: the mismatch repair cancer syndrome (or constitutional mismatch repair deficiency, CMMR-D), manifesting as multiple occurrences of tumors at an early age, often colon and brain tumors.{{OMIM|276300}}

Sporadic cancers with a DNA repair deficiency only rarely have a mutation in a DNA repair gene, but they instead tend to have epigenetic alterations such as promoter methylation that inhibit DNA repair gene expression.{{cite journal | vauthors = Bernstein C, Bernstein H | title = Epigenetic reduction of DNA repair in progression to gastrointestinal cancer | journal = World Journal of Gastrointestinal Oncology | volume = 7 | issue = 5 | pages = 30–46 | date = May 2015 | pmid = 25987950 | pmc = 4434036 | doi = 10.4251/wjgo.v7.i5.30 | doi-access = free }} About 13% of colorectal cancers are deficient in DNA mismatch repair, commonly due to loss of MLH1 (9.8%), or sometimes MSH2, MSH6 or PMS2 (all ≤1.5%).{{cite journal | vauthors = Truninger K, Menigatti M, Luz J, Russell A, Haider R, Gebbers JO, Bannwart F, Yurtsever H, Neuweiler J, Riehle HM, Cattaruzza MS, Heinimann K, Schär P, Jiricny J, Marra G | display-authors = 6 | title = Immunohistochemical analysis reveals high frequency of PMS2 defects in colorectal cancer | journal = Gastroenterology | volume = 128 | issue = 5 | pages = 1160–71 | date = May 2005 | pmid = 15887099 | doi = 10.1053/j.gastro.2005.01.056 | doi-access = free }} For most MLH1-deficient sporadic colorectal cancers, the deficiency was due to MLH1 promoter methylation. Other cancer types have higher frequencies of MLH1 loss (see table below), which are again largely a result of methylation of the promoter of the MLH1 gene. A different epigenetic mechanism underlying MMR deficiencies might involve over-expression of a microRNA, for example miR-155 levels inversely correlate with expression of MLH1 or MSH2 in colorectal cancer.{{cite journal | vauthors = Valeri N, Gasparini P, Fabbri M, Braconi C, Veronese A, Lovat F, Adair B, Vannini I, Fanini F, Bottoni A, Costinean S, Sandhu SK, Nuovo GJ, Alder H, Gafa R, Calore F, Ferracin M, Lanza G, Volinia S, Negrini M, McIlhatton MA, Amadori D, Fishel R, Croce CM | display-authors = 6 | title = Modulation of mismatch repair and genomic stability by miR-155 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 15 | pages = 6982–7 | date = April 2010 | pmid = 20351277 | pmc = 2872463 | doi = 10.1073/pnas.1002472107 | bibcode = 2010PNAS..107.6982V | doi-access = free }}

A field defect (field cancerization) is an area of epithelium that has been preconditioned by epigenetic or genetic changes, predisposing it towards development of cancer. As pointed out by Rubin " ...there is evidence that more than 80% of the somatic mutations found in mutator phenotype human colorectal tumors occur before the onset of terminal clonal expansion."{{cite journal | vauthors = Rubin H | title = Fields and field cancerization: the preneoplastic origins of cancer: asymptomatic hyperplastic fields are precursors of neoplasia, and their progression to tumors can be tracked by saturation density in culture | journal = BioEssays | volume = 33 | issue = 3 | pages = 224–31 | date = March 2011 | pmid = 21254148 | doi = 10.1002/bies.201000067 | s2cid = 44981539 }}{{cite journal | vauthors = Tsao JL, Yatabe Y, Salovaara R, Järvinen HJ, Mecklin JP, Aaltonen LA, Tavaré S, Shibata D | display-authors = 6 | title = Genetic reconstruction of individual colorectal tumor histories | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 3 | pages = 1236–41 | date = February 2000 | pmid = 10655514 | pmc = 15581 | doi = 10.1073/pnas.97.3.1236 | bibcode = 2000PNAS...97.1236T | doi-access = free }} Similarly, Vogelstein et al.{{cite journal | vauthors = Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA, Kinzler KW | title = Cancer genome landscapes | journal = Science | volume = 339 | issue = 6127 | pages = 1546–58 | date = March 2013 | pmid = 23539594 | pmc = 3749880 | doi = 10.1126/science.1235122 | bibcode = 2013Sci...339.1546V }} point out that more than half of somatic mutations identified in tumors occurred in a pre-neoplastic phase (in a field defect), during growth of apparently normal cells.

MLH1 deficiencies were common in the field defects (histologically normal tissues) surrounding tumors; see Table above. Epigenetically silenced or mutated MLH1 would likely not confer a selective advantage upon a stem cell, however, it would cause increased mutation rates, and one or more of the mutated genes may provide the cell with a selective advantage. The deficientMLH1 gene could then be carried along as a selectively near-neutral passenger (hitch-hiker) gene when the mutated stem cell generates an expanded clone. The continued presence of a clone with an epigenetically repressed MLH1 would continue to generate further mutations, some of which could produce a tumor.

MMR and mismatch repair mutations were initially observed to associate with immune checkpoint blockade efficacy in a study examining responders to anti-PD1.{{cite journal |last1=Rizvi |first1=Naiyer |last2=Hellmann |first2=Matthew |last3=Snyder |first3=Alexandra |last4=Kvistborg |first4=Pia |last5=Makarov |first5=Vladimir |last6=Havel |first6=Jonathan |last7=Lee |first7=William |last8=Yuan |first8=Jianda |last9=Wong |first9=Phillip |last10=Ho |first10=Teresa |last11=Miller |first11=Martin |last12=Rekhtman |first12=Natasha |last13=Moreira |first13=Andra |last14=Ibrahim |first14=Fawzia |last15=Bruggeman |first15=Cameron |last16=Gasmi |first16=Billel |last17=Zappasodi |first17=Roberta |last18=Maeda |first18=Yuka |last19=Sander |first19=Chris |last20=Garon |first20=Edward |last21=Merghoub |first21=Taha |last22=Wolchok |first22=Jedd |last23=Schumacher |first23=Ton |last24=Timothy |first24=Chan |title=Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer |journal=Science |date=2015 |volume=6230 |issue=348 |pages=124–128 |doi=10.1126/science.aaa1348 |pmid=25765070 |pmc=4993154 |bibcode=2015Sci...348..124R }} The association between MSI positivity and positive response to anti-PD1 was subsequently validated in a prospective clinical trial and approved by the FDA.{{Cite web|url=https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm560040.htm|archive-url=https://web.archive.org/web/20170606185340/https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm560040.htm|url-status=dead|archive-date=June 6, 2017|title=Approved Drugs –FDA grants accelerated approval to pembrolizumab for first tissue/site agnostic indication | author = Center for Drug Evaluation and Research|website=www.fda.gov|language=en|access-date=2017-05-24}}

In humans, seven DNA mismatch repair (MMR) proteins (MLH1, MLH3, MSH2, MSH3, MSH6, PMS1 and PMS2) work coordinately in sequential steps to initiate repair of DNA mismatches.{{cite journal | vauthors = Pal T, Permuth-Wey J, Sellers TA | title = A review of the clinical relevance of mismatch-repair deficiency in ovarian cancer | journal = Cancer | volume = 113 | issue = 4 | pages = 733–42 | date = August 2008 | pmid = 18543306 | pmc = 2644411 | doi = 10.1002/cncr.23601 }} In addition, there are Exo1-dependent and Exo1-independent MMR subpathways.{{cite journal | vauthors = Goellner EM, Putnam CD, Kolodner RD | title = Exonuclease 1-dependent and independent mismatch repair | journal = DNA Repair | volume = 32 | pages = 24–32 | date = August 2015 | pmid = 25956862 | pmc = 4522362 | doi = 10.1016/j.dnarep.2015.04.010 }}

Other gene products involved in mismatch repair (subsequent to initiation by MMR genes) in humans include DNA polymerase delta, PCNA, RPA, HMGB1, RFC and DNA ligase I, plus histone and chromatin modifying factors.{{cite journal | vauthors = Li GM | title = Mechanisms and functions of DNA mismatch repair | journal = Cell Research | volume = 18 | issue = 1 | pages = 85–98 | date = January 2008 | pmid = 18157157 | doi = 10.1038/cr.2007.115 | doi-access = free }}{{cite journal | vauthors = Li GM | title = New insights and challenges in mismatch repair: getting over the chromatin hurdle | journal = DNA Repair | volume = 19 | pages = 48–54 | date = July 2014 | pmid = 24767944 | pmc = 4127414 | doi = 10.1016/j.dnarep.2014.03.027 }}

In certain circumstances, the MMR pathway may recruit an error-prone DNA polymerase eta (POLH). This happens in B-lymphocytes during somatic hypermutation, where POLH is used to introduce genetic variation into antibody genes.{{cite journal | vauthors = Chahwan R, Edelmann W, Scharff MD, Roa S | title = AIDing antibody diversity by error-prone mismatch repair | journal = Seminars in Immunology | volume = 24 | issue = 4 | pages = 293–300 | date = August 2012 | pmid = 22703640 | pmc = 3422444 | doi = 10.1016/j.smim.2012.05.005 }} However, this error-prone MMR pathway may be triggered in other types of human cells upon exposure to genotoxins {{cite journal | vauthors = Hsieh P | title = DNA mismatch repair: Dr. Jekyll and Mr. Hyde? | journal = Molecular Cell | volume = 47 | issue = 5 | pages = 665–6 | date = September 2012 | pmid = 22980456 | pmc = 3457060 | doi = 10.1016/j.molcel.2012.08.020 }} and indeed it is broadly active in various human cancers, causing mutations that bear a signature of POLH activity.{{cite journal | vauthors = Supek F, Lehner B | title = Clustered Mutation Signatures Reveal that Error-Prone DNA Repair Targets Mutations to Active Genes | journal = Cell | volume = 170 | issue = 3 | pages = 534–547.e23 | date = July 2017 | pmid = 28753428 | doi = 10.1016/j.cell.2017.07.003 | doi-access = free | hdl = 10230/35343 | hdl-access = free }}

Recognizing and repairing mismatches and indels is important for cells because failure to do so results in microsatellite instability (MSI) and an elevated spontaneous mutation rate (mutator phenotype). In comparison to other cancer types, MMR-deficient (MSI) cancer has a very high frequency of mutations, close to melanoma and lung cancer,{{cite journal | vauthors = Tuna M, Amos CI | title = Genomic sequencing in cancer | journal = Cancer Letters | volume = 340 | issue = 2 | pages = 161–70 | date = November 2013 | pmid = 23178448 | pmc = 3622788 | doi = 10.1016/j.canlet.2012.11.004 }} cancer types caused by much exposure to UV radiation and mutagenic chemicals.

In addition to a very high mutation burden, MMR deficiencies result in an unusual distribution of somatic mutations across the human genome: this suggests that MMR preferentially protects the gene-rich, early-replicating euchromatic regions.{{cite journal | vauthors = Supek F, Lehner B | title = Differential DNA mismatch repair underlies mutation rate variation across the human genome | journal = Nature | volume = 521 | issue = 7550 | pages = 81–4 | date = May 2015 | pmid = 25707793 | pmc = 4425546 | doi = 10.1038/nature14173 | bibcode = 2015Natur.521...81S }} In contrast, the gene-poor, late-replicating heterochromatic genome regions exhibit high mutation rates in many human tumors.{{cite journal | vauthors = Schuster-Böckler B, Lehner B | title = Chromatin organization is a major influence on regional mutation rates in human cancer cells | journal = Nature | volume = 488 | issue = 7412 | pages = 504–7 | date = August 2012 | pmid = 22820252 | doi = 10.1038/nature11273 | bibcode = 2012Natur.488..504S | s2cid = 205229634 }}

The histone modification H3K36me3, an epigenetic mark of active chromatin, has the ability to recruit the MSH2-MSH6 (hMutSα) complex.{{cite journal | vauthors = Li F, Mao G, Tong D, Huang J, Gu L, Yang W, Li GM | title = The histone mark H3K36me3 regulates human DNA mismatch repair through its interaction with MutSα | journal = Cell | volume = 153 | issue = 3 | pages = 590–600 | date = April 2013 | pmid = 23622243 | pmc = 3641580 | doi = 10.1016/j.cell.2013.03.025 }} Consistently, regions of the human genome with high levels of H3K36me3 accumulate less mutations due to MMR activity.

Lack of MMR often occurs in coordination with loss of other DNA repair genes. For example, MMR genes MLH1 and MLH3 as well as 11 other DNA repair genes (such as MGMT and many NER pathway genes) were significantly down-regulated in lower grade as well as in higher grade astrocytomas, in contrast to normal brain tissue.{{cite journal | vauthors = Jiang Z, Hu J, Li X, Jiang Y, Zhou W, Lu D | title = Expression analyses of 27 DNA repair genes in astrocytoma by TaqMan low-density array | journal = Neuroscience Letters | volume = 409 | issue = 2 | pages = 112–7 | date = December 2006 | pmid = 17034947 | doi = 10.1016/j.neulet.2006.09.038 | s2cid = 54278905 }} Moreover, MLH1 and MGMT expression was closely correlated in 135 specimens of gastric cancer and loss of MLH1 and MGMT appeared to be synchronously accelerated during tumor progression.{{cite journal | vauthors = Kitajima Y, Miyazaki K, Matsukura S, Tanaka M, Sekiguchi M | title = Loss of expression of DNA repair enzymes MGMT, hMLH1, and hMSH2 during tumor progression in gastric cancer | journal = Gastric Cancer | volume = 6 | issue = 2 | pages = 86–95 | year = 2003 | pmid = 12861399 | doi = 10.1007/s10120-003-0213-z | doi-access = free }}

Deficient expression of multiple DNA repair genes is often found in cancers, and may contribute to the thousands of mutations usually found in cancers (see Mutation frequencies in cancers).

Although several DNA repair pathways have been reported to occur in the mitochondria, currently the DNA mismatch repair pathway is the pathway that is most comprehensively described.{{cite journal |vauthors=Saki M, Prakash A |title=DNA damage related crosstalk between the nucleus and mitochondria |journal=Free Radic Biol Med |volume=107 |issue= |pages=216–227 |date=June 2017 |pmid=27915046 |pmc=5449269 |doi=10.1016/j.freeradbiomed.2016.11.050 |url=}} The proteins acting in the maintenance of mitochondrial DNA are encoded by nuclear genes and translocated to the mitochondria. The mitochondria of human cells are able to repair DNA base pair mismatches using a pathway that is distinct from the DNA mismatch repair pathway of the nucleus.deSouza-Pinto NC, Mason PA, Hashiguchi K, Weissman L, Tian J, Guay D, Lebel M, Stevnsner TV, Rasmussen LJ, Bohr VA. Novel DNA mismatch-repair activity involving YB-1 in human mitochondria. DNA Repair (Amst). 2009 Jun 4;8(6):704-19. doi: 10.1016/j.dnarep.2009.01.021. Epub 2009 Mar 9. PMID: 19272840; PMCID: PMC2693314. This distinct mitochondrial mismatch repair pathway includes the activity of the Y box binding protein 1 (designated YB-1 or YBX1), that is considered to act in the mismatch binding and recognition steps of mismatch repair. DNA repair mechanisms that are specific to the mitochondria may reflect the proximity of the mitochondrial DNA to the system of oxidative phosphorylation and consequently to the DNA-damaging reactive oxygen species formed in association with ATP production.{{cite journal |vauthors=Bazzani V, Equisoain Redin M, McHale J, Perrone L, Vascotto C |title=Mitochondrial DNA Repair in Neurodegenerative Diseases and Ageing |journal=Int J Mol Sci |volume=23 |issue=19 |date=September 2022 |page=11391 |pmid=36232693 |pmc=9569545 |doi=10.3390/ijms231911391 |doi-access=free |url=}}

A popular idea, that has failed to gain significant experimental support, is the idea that mutation, as distinct from DNA damage, is the primary cause of aging. Mice defective in the mutL homolog Pms2 have about a 100-fold elevated mutation frequency in all tissues, but do not appear to age more rapidly.{{cite journal | vauthors = Narayanan L, Fritzell JA, Baker SM, Liskay RM, Glazer PM | title = Elevated levels of mutation in multiple tissues of mice deficient in the DNA mismatch repair gene Pms2 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 7 | pages = 3122–7 | date = April 1997 | pmid = 9096356 | pmc = 20332 | doi = 10.1073/pnas.94.7.3122 | bibcode = 1997PNAS...94.3122N | doi-access = free }} These mice display mostly normal development and life, except for early onset carcinogenesis and male infertility.

{{Portal|Biology}}

• Base excision repair
• Nucleotide excision repair

{{reflist|33em}}

{{refbegin|33em}}

• {{cite journal | vauthors = Hsieh P, Yamane K | title = DNA mismatch repair: molecular mechanism, cancer, and ageing | journal = Mechanisms of Ageing and Development | volume = 129 | issue = 7–8 | pages = 391–407 | year = 2008 | pmid = 18406444 | pmc = 2574955 | doi = 10.1016/j.mad.2008.02.012 }}
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• {{cite book | vauthors = Joseph N, Duppatla V, Rao DN | title = Prokaryotic DNA mismatch repair | journal = Progress in Nucleic Acid Research and Molecular Biology | volume = 81 | pages = 1–49 | year = 2006 | pmid = 16891168 | doi = 10.1016/S0079-6603(06)81001-9 | isbn = 9780125400817 }}
• {{cite journal | vauthors = Yang W | title = Structure and function of mismatch repair proteins | journal = Mutation Research | volume = 460 | issue = 3–4 | pages = 245–56 | date = August 2000 | pmid = 10946232 | doi = 10.1016/s0921-8777(00)00030-6 | url = https://zenodo.org/record/1260137 }}
• {{cite book | vauthors = Griffiths JF, Gilbert WM, Lewontin RC, Wessler SR, Suzuki DT, Miller JH | title = An introduction to genetic analysis | date = 2004 | publisher = Freeman | location = New York, NY | isbn = 978-0-7167-4939-4 | edition = 8th }}
• {{cite journal | vauthors = Kunkel TA, Erie DA | title = DNA mismatch repair | journal = Annual Review of Biochemistry | volume = 74 | pages = 681–710 | year = 2005 | pmid = 15952900 | doi = 10.1146/annurev.biochem.74.082803.133243 | url = https://zenodo.org/record/1234939 }}
• {{cite book | vauthors = Friedberg EC, Walker GC, Siede W, Wood RD, Schultz RA, Ellenberger | author-link4 = Richard D. Wood | title = DNA repair and mutagenesis | date = 2005 | publisher = ASM Press | location = Washington, D.C. | isbn = 978-1-55581-319-2 | edition = 2nd }}

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• [http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/D/DNArepair.html DNA Repair] {{Webarchive|url=https://web.archive.org/web/20180212073520/http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/D/DNArepair.html |date=2018-02-12 }}
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{{DNA repair}}

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Category:DNA repair

Category:Mutation