dna mismatch repair


Summary: A DNA repair pathway involved in correction of errors introduced during DNA replication when an incorrect base, which cannot form hydrogen bonds with the corresponding base in the parent strand, is incorporated into the daughter strand. Excinucleases recognize the BASE PAIR MISMATCH and cause a segment of polynucleotide chain to be excised from the daughter strand, thereby removing the mismatched base. (from Oxford Dictionary of Biochemistry and Molecular Biology, 2001)

Top Publications

  1. Overman M, McDermott R, Leach J, Lonardi S, Lenz H, Morse M, et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol. 2017;18:1182-1191 pubmed publisher
    Metastatic DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer has a poor prognosis after treatment with conventional chemotherapy and exhibits high levels of tumour neoantigens, tumour-..
  2. Chen S, Huang T, Zhou Y, Han Y, Xu M, Gu J. AfterQC: automatic filtering, trimming, error removing and quality control for fastq data. BMC Bioinformatics. 2017;18:80 pubmed publisher
    ..While providing rich configurable options, AfterQC can detect and set all the options automatically and require no argument in most cases. ..
  3. Maiuri A, Peng M, Podicheti R, Sriramkumar S, Kamplain C, Rusch D, et al. Mismatch Repair Proteins Initiate Epigenetic Alterations during Inflammation-Driven Tumorigenesis. Cancer Res. 2017;77:3467-3478 pubmed publisher
    ..Understanding such mechanisms will inform development of pharmacotherapies to reduce carcinogenesis. Cancer Res; 77(13); 3467-78. ©2017 AACR. ..
  4. Westdorp H, Kolders S, Hoogerbrugge N, de Vries I, Jongmans M, Schreibelt G. Immunotherapy holds the key to cancer treatment and prevention in constitutional mismatch repair deficiency (CMMRD) syndrome. Cancer Lett. 2017;403:159-164 pubmed publisher
    Monoallelic germline mutations in one of the DNA mismatch repair (MMR) genes cause Lynch syndrome, with a high lifetime risks of colorectal and endometrial cancer at adult age...
  5. Ruiz J, Alvarez Cubero M, Rosado F, Espín E, Bernal C. Confirmed pathogenic effect of a splice site variation in the MLH1 gene causing Lynch syndrome. Int J Colorectal Dis. 2014;29:1019-20 pubmed publisher
  6. Fukui K, Iino H, Baba S, Kumasaka T, Kuramitsu S, Yano T. Crystal structure and DNA-binding property of the ATPase domain of bacterial mismatch repair endonuclease MutL from Aquifex aeolicus. Biochim Biophys Acta Proteins Proteom. 2017;1865:1178-1187 pubmed publisher
    b>DNA mismatch repair (MMR) system corrects mismatched bases that are generated mainly by DNA replication errors. The repair system excises the error-containing single-stranded region and enables the re-synthesis of the strand...
  7. Ford J. Is breast cancer a part of Lynch syndrome?. Breast Cancer Res. 2012;14:110 pubmed publisher
    ..These results have important implications for genetic counseling and genetic testing of families with breast cancer and other tumors associated with Lynch syndrome, such as colorectal and endometrial cancers. ..
  8. Kim K, Lee T, Kim J, Cho N, Kim W, Kang G. Deletion in HSP110 T17: correlation with wild-type HSP110 expression and prognostic significance in microsatellite-unstable advanced gastric cancers. Hum Pathol. 2017;67:109-118 pubmed publisher
    ..Large HSP110 T17 was not a prognostic indicator in MSI-H GCs. ..
  9. Cosgrove C, Cohn D, Hampel H, Frankel W, Jones D, McElroy J, et al. Epigenetic silencing of MLH1 in endometrial cancers is associated with larger tumor volume, increased rate of lymph node positivity and reduced recurrence-free survival. Gynecol Oncol. 2017;146:588-595 pubmed publisher
    ..MMR testing that includes MLH1 methylation analysis defines a subset of tumors that have worse prognostic features and reduced RFS. ..

More Information


  1. Peres J. To screen or not to screen for Lynch syndrome. J Natl Cancer Inst. 2010;102:1382-4 pubmed publisher
  2. Nebot Bral L, Brandao D, Verlingue L, Rouleau E, Caron O, Despras E, et al. Hypermutated tumours in the era of immunotherapy: The paradigm of personalised medicine. Eur J Cancer. 2017;84:290-303 pubmed publisher
    ..This breakthrough represents a turning point in the management of these hypermutated tumours and paves the way for broader strategies in immunoprecision medicine. ..
  3. LARREA A, Lujan S, Kunkel T. SnapShot: DNA mismatch repair. Cell. 2010;141:730.e1 pubmed publisher
  4. Vargas Parra G, González Acosta M, Thompson B, Gómez C, Fernández A, Dámaso E, et al. Elucidating the molecular basis of MSH2-deficient tumors by combined germline and somatic analysis. Int J Cancer. 2017;141:1365-1380 pubmed publisher
    ..In conclusion, our comprehensive strategy combining germline and somatic mutational status of CRC-associated genes by means of a subexome panel allows the elucidation of up to 86% of MSH2-deficient suspected LS tumors. ..
  5. Sunga A, Ricker C, Espenschied C, Castillo D, Melas M, Herzog J, et al. Spectrum of mismatch repair gene mutations and clinical presentation of Hispanic individuals with Lynch syndrome. Cancer Genet. 2017;212-213:1-7 pubmed publisher
    ..This is the largest report of Hispanic MMR mutations in North America; however, a larger sample and haplotype analyses are needed to better understand recurrent MMR mutations in Hispanic populations. ..
  6. Andrianova M, Chetan G, Sibin M, McKee T, Merkler D, Narasinga R, et al. Germline PMS2 and somatic POLE exonuclease mutations cause hypermutability of the leading DNA strand in biallelic mismatch repair deficiency syndrome brain tumours. J Pathol. 2017;243:331-341 pubmed publisher
    ..Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. ..
  7. Li P, Xiao Z, Braciak T, Ou Q, Chen G, Oduncu F. Systematic immunohistochemical screening for mismatch repair and ERCC1 gene expression from colorectal cancers in China: Clinicopathological characteristics and effects on survival. PLoS ONE. 2017;12:e0181615 pubmed publisher
    ..We also found the determination of ERCC1 expression to be useful for predicting DFS or OS for stage II and III CRC patients. In addition, the expression of MMR genes and ERCC1 showed a significant relationship. ..
  8. Al Sweel N, Raghavan V, Dutta A, Ajith V, Di Vietro L, Khondakar N, et al. mlh3 mutations in baker's yeast alter meiotic recombination outcomes by increasing noncrossover events genome-wide. PLoS Genet. 2017;13:e1006974 pubmed publisher
    ..It also plays a minor role in eukaryotic DNA mismatch repair (MMR)...
  9. Yuan L, Wang J, Zhu K, Yang M, Gu W, Lai C, et al. A highly malignant case of neuroblastoma with substantial increase of single-nucleotide variants and normal mismatch repair system: A case report. Medicine (Baltimore). 2017;96:e8845 pubmed publisher
    ..Both NGS and immunohistochemistry (IHC) analysis indicated that DNA mismatch repair (MMR) system was intact...
  10. Russo M, Broach J, Sheldon K, Houser K, Liu D, Kesterson J, et al. Clonal evolution in paired endometrial intraepithelial neoplasia/atypical hyperplasia and endometrioid adenocarcinoma. Hum Pathol. 2017;67:69-77 pubmed publisher
    ..These findings indicate that EIN/AH gives rise to endometrioid adenocarcinoma by a complex process of subclone evolution, not a linear accumulation of molecular events. ..
  11. Ricker C, Hanna D, Peng C, Nguyen N, Stern M, Schmit S, et al. DNA mismatch repair deficiency and hereditary syndromes in Latino patients with colorectal cancer. Cancer. 2017;123:3732-3743 pubmed publisher
    ..Cancer 2017. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. Cancer 2017;123:3732-3743. © 2017 American Cancer Society. ..
  12. Liu D, Frederiksen J, Liberti S, Lützen A, Keijzers G, Pena Diaz J, et al. Human DNA polymerase delta double-mutant D316A;E318A interferes with DNA mismatch repair in vitro. Nucleic Acids Res. 2017;45:9427-9440 pubmed publisher
    b>DNA mismatch repair (MMR) is a highly-conserved DNA repair mechanism, whose primary role is to remove DNA replication errors preventing them from manifesting as mutations, thereby increasing the overall genome stability...
  13. Tangjitgamol S, Kittisiam T, Tanvanich S. Prevalence and prognostic role of mismatch repair gene defect in endometrial cancer patients. Tumour Biol. 2017;39:1010428317725834 pubmed publisher
    ..The patients with mismatch repair gene defect had significantly younger age (? 60 years) and better prognosis in terms of early stage, negative nodal status, and longer survivals. ..
  14. Thompson B, Spurdle A, Plazzer J, Greenblatt M, Akagi K, Al Mulla F, et al. Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database. Nat Genet. 2014;46:107-115 pubmed publisher
  15. Storb U, Shen H, Nicolae D. Somatic hypermutation: processivity of the cytosine deaminase AID and error-free repair of the resulting uracils. Cell Cycle. 2009;8:3097-101 pubmed
  16. Wimmer K, Kratz C. Constitutional mismatch repair-deficiency syndrome. Haematologica. 2010;95:699-701 pubmed publisher
  17. Panyutin I, Panyutin I, Powell Castilla I, Felix L, Neumann R. Single nucleotide variations in cultured cancer cells: Effect of mismatch repair. Mutat Res. 2017;803-805:22-25 pubmed publisher
    ..Our data demonstrate that the extent of genetic variation at the single nucleotide level in cultured cancer cells is significantly affected by the status of the DNA mismatch repair system.
  18. Quessada Vial A, van Oijen A. How DNA-repair proteins find their targets. Proc Natl Acad Sci U S A. 2012;109:18243-4 pubmed publisher
  19. Pecina Slaus N, Kafka A, Bukovac A, Vladusić T, Tomas D, Hrascan R. Genetic changes of MLH1 and MSH2 genes could explain constant findings on microsatellite instability in intracranial meningioma. Tumour Biol. 2017;39:1010428317705791 pubmed publisher
    ..14; p?=?0.01). Our study contributes to better understanding of the genetic profile of human intracranial meningiomas and suggests that meningiomas harbor defective cellular DNA mismatch repair mechanisms.
  20. Dalia T, Yoon S, Galli E, Barre F, Waters C, Dalia A. Enhancing multiplex genome editing by natural transformation (MuGENT) via inactivation of ssDNA exonucleases. Nucleic Acids Res. 2017;45:7527-7537 pubmed publisher
    ..Thus, rational removal of ssDNA exonucleases may be broadly applicable for enhancing the efficacy and ease of MuGENT in diverse naturally transformable species. ..
  21. Cheyuo C, Radwan W, Ahn J, Gyure K, Qaiser R, Tomboc P. Biallelic PMS2 Mutation and Heterozygous DICER1 Mutation Presenting as Constitutional Mismatch Repair Deficiency With Corpus Callosum Agenesis: Case Report and Review of Literature. J Pediatr Hematol Oncol. 2017;39:e381-e387 pubmed publisher
    ..This report is the first to allude to a possible interaction of the mismatch repair system with DICER1 to cause corpus callosum agenesis. ..
  22. Alnabulsi A, Swan R, Cash B, Alnabulsi A, Murray G. The differential expression of omega-3 and omega-6 fatty acid metabolising enzymes in colorectal cancer and its prognostic significance. Br J Cancer. 2017;116:1612-1620 pubmed publisher
    ..046). A significant and independent association has been identified between overall survival and the differential expression of CYP4A11 and CYP4F11 in the whole patient cohort and in mismatch repair-proficient tumours. ..
  23. Proctor L, Pradhan M, Leung S, Cheng A, Lee C, Soslow R, et al. Assessment of DNA Ploidy in the ProMisE molecular subgroups of endometrial cancer. Gynecol Oncol. 2017;146:596-602 pubmed publisher
    ..The addition of ploidy to the ProMisE molecular categories conferred additional prognostic value within the MMR-D group, which merits further study. ..
  24. Fricke F, Lee J, Michalak M, Warnken U, Hausser I, Suarez Carmona M, et al. TGFBR2-dependent alterations of exosomal cargo and functions in DNA mismatch repair-deficient HCT116 colorectal cancer cells. Cell Commun Signal. 2017;15:14 pubmed publisher
    Colorectal cancers (CRCs) that lack DNA mismatch repair function exhibit the microsatellite unstable (MSI) phenotype and are characterized by the accumulation of frameshift mutations at short repetitive DNA sequences (microsatellites)...
  25. Martins Pinheiro M, Oliveira A, Valencia A, Fernández Silva F, Silva L, Lopes Kulishev C, et al. Molecular characterization of Caulobacter crescentus mutator strains. Gene. 2017;626:251-257 pubmed publisher
    ..In spite of the limitations of using a single marker, possible reasons for the observed mutational bias are discussed in the light of the repertoire of DNA repair genes in this bacterium. ..
  26. Palecek E, Bartošík M. Electrochemistry of nucleic acids. Chem Rev. 2012;112:3427-81 pubmed publisher
  27. Wright M, Beaty J, Ternent C. Molecular Markers for Colorectal Cancer. Surg Clin North Am. 2017;97:683-701 pubmed publisher
    ..Techniques to recognize colorectal cancer at the molecular level have facilitated development of new signature drugs designed to inhibit the unique pathways of colorectal cancer growth and immunity. ..
  28. Espenschied C, Laduca H, Li S, McFarland R, Gau C, Hampel H. Multigene Panel Testing Provides a New Perspective on Lynch Syndrome. J Clin Oncol. 2017;35:2568-2575 pubmed publisher
    ..These data also highlight the limitations of current testing criteria in identifying these patients, as well as the need for further investigation of cancer risks in patients with MMR mutations. ..
  29. Teply B, Antonarakis E. Treatment strategies for DNA repair-deficient prostate cancer. Expert Rev Clin Pharmacol. 2017;10:889-898 pubmed publisher
    ..Finally, optimal strategies to sequence or combine targeted agents for these patients with 'actionable' mutations are now needed. ..
  30. Drost J, van Boxtel R, Blokzijl F, Mizutani T, Sasaki N, Sasselli V, et al. Use of CRISPR-modified human stem cell organoids to study the origin of mutational signatures in cancer. Science. 2017;358:234-238 pubmed publisher
    ..We show that signature 30 can arise from germline NTHL1 mutations. ..
  31. Raats D, Frenkel N, van Schelven S, Rinkes I, Laoukili J, Kranenburg O. CD95 ligand induces senescence in mismatch repair-deficient human colon cancer via chronic caspase-mediated induction of DNA damage. Cell Death Dis. 2017;8:e2669 pubmed publisher
    ..We conclude that induction of senescence is a hitherto unrecognized consequence of high CD95 expression, which appears to be most relevant for CMS1. ..
  32. Kerr D, Midgley R. Defective mismatch repair in colon cancer: a prognostic or predictive biomarker?. J Clin Oncol. 2010;28:3210-2 pubmed publisher
  33. Samstein R, Chan T. Dissecting microsatellite instability in colorectal cancer: one size does not fit all. Genome Med. 2017;9:45 pubmed publisher
    ..See related research by Sveen et al. 10.1186/s13073-017-0434-0. ..
  34. Feliziani S, Luján A, Moyano A, Sola C, Bocco J, Montanaro P, et al. Mucoidy, quorum sensing, mismatch repair and antibiotic resistance in Pseudomonas aeruginosa from cystic fibrosis chronic airways infections. PLoS ONE. 2010;5: pubmed publisher
    ..and MexZ (multidrug-efflux pump MexXY) are the most frequently observed, with those inactivating the DNA mismatch repair system (MRS) being also highly prevalent in P...
  35. Jee J, Rasouly A, Shamovsky I, Akivis Y, Steinman S, Mishra B, et al. Rates and mechanisms of bacterial mutagenesis from maximum-depth sequencing. Nature. 2016;534:693-6 pubmed
  36. Dahal B, Kadyrova L, Delfino K, Rogozin I, Gujar V, Lobachev K, et al. Involvement of DNA mismatch repair in the maintenance of heterochromatic DNA stability in Saccharomyces cerevisiae. PLoS Genet. 2017;13:e1007074 pubmed publisher
    ..We show here that in the yeast Saccharomyces cerevisiae (i) DNA mismatch repair (MMR) is required for the maintenance of heterochromatic DNA stability, (ii) MutL? (Mlh1-Pms1 heterodimer), ..
  37. Boland C, Shike M. Report from the Jerusalem workshop on Lynch syndrome-hereditary nonpolyposis colorectal cancer. Gastroenterology. 2010;138:2197.e1-7 pubmed publisher
  38. Liu D, Keijzers G, Rasmussen L. DNA mismatch repair and its many roles in eukaryotic cells. Mutat Res. 2017;773:174-187 pubmed publisher
    b>DNA mismatch repair (MMR) is an important DNA repair pathway that plays critical roles in DNA replication fidelity, mutation avoidance and genome stability, all of which contribute significantly to the viability of cells and organisms...
  39. Fernández Rozadilla C, Brea Fernández A, Bessa X, Alvarez Urturi C, Abuli A, Clofent J, et al. BMPR1A mutations in early-onset colorectal cancer with mismatch repair proficiency. Clin Genet. 2013;84:94-6 pubmed publisher
  40. Libera L, Sahnane N, Carnevali I, Cimetti L, Cerutti R, Chiaravalli A, et al. Microsatellite analysis of sporadic and hereditary gynaecological cancer in routine diagnostics. J Clin Pathol. 2017;70:792-797 pubmed publisher
    ..i>RPL22 and SRPR testing may be useful to integrate MRP panel for the analysis of critical cases. ..
  41. Nieminen T, Abdel Rahman W, Ristimaki A, Lappalainen M, Lahermo P, Mecklin J, et al. BMPR1A mutations in hereditary nonpolyposis colorectal cancer without mismatch repair deficiency. Gastroenterology. 2011;141:e23-6 pubmed publisher
  42. Nickoloff J, Jones D, Lee S, Williamson E, Hromas R. Drugging the Cancers Addicted to DNA Repair. J Natl Cancer Inst. 2017;109: pubmed publisher
    ..In addition, future therapies will exploit artificial synthetic lethality, where complementary DNA repair pathways are targeted simultaneously in cancers without DNA repair defects. ..
  43. Garber K. Oncologists await historic first: a pan-tumor predictive marker, for immunotherapy. Nat Biotechnol. 2017;35:297-298 pubmed publisher
  44. Davies H, Morganella S, Purdie C, Jang S, Borgen E, Russnes H, et al. Whole-Genome Sequencing Reveals Breast Cancers with Mismatch Repair Deficiency. Cancer Res. 2017;77:4755-4762 pubmed publisher
    ..i>Cancer Res; 77(18); 4755-62. ©2017 AACR. ..
  45. Supek F, Lehner B. Clustered Mutation Signatures Reveal that Error-Prone DNA Repair Targets Mutations to Active Genes. Cell. 2017;170:534-547.e23 pubmed publisher
    ..Carcinogens and error-prone repair therefore redistribute mutations to the more important regions of the genome, contributing a substantial mutation load in many tumors, including driver mutations. ..
  46. Bartley A, Hamilton S, Alsabeh R, Ambinder E, Berman M, COLLINS E, et al. Template for reporting results of biomarker testing of specimens from patients with carcinoma of the colon and rectum. Arch Pathol Lab Med. 2014;138:166-70 pubmed publisher
  47. Chen W, Swanson B, Frankel W. Molecular genetics of microsatellite-unstable colorectal cancer for pathologists. Diagn Pathol. 2017;12:24 pubmed publisher
    Microsatellite-unstable colorectal cancers (CRC) that are due to deficient DNA mismatch repair (dMMR) represent approximately 15% of all CRCs in the United States...
  48. Claeys Bouuaert C, Keeney S. Distinct DNA-binding surfaces in the ATPase and linker domains of MutL? determine its substrate specificities and exert separable functions in meiotic recombination and mismatch repair. PLoS Genet. 2017;13:e1006722 pubmed publisher
    ..Taken together, our results offer insights into the structure-function relationships of the MutL? complex and reveal unanticipated genetic relationships between components of the meiotic recombination machinery. ..
  49. Villahermosa D, Christensen O, Knapp K, Fleck O. Schizosaccharomyces pombe MutS? and MutL? Maintain Stability of Tetra-Nucleotide Repeats and Msh3 of Hepta-Nucleotide Repeats. G3 (Bethesda). 2017;7:1463-1473 pubmed publisher
    ..We conclude that Msh3 has no obvious function in MMR in S. pombe, but contributes to DNA repeat stability in MMR-independent processes. ..
  50. Stark A, Doukas A, Hugo H, Hedderich J, Hattermann K, Maximilian Mehdorn H, et al. Expression of DNA mismatch repair proteins MLH1, MSH2, and MSH6 in recurrent glioblastoma. Neurol Res. 2015;37:95-105 pubmed publisher
    ..The immunohistochemical expression of MLH1, MSH2, and MSH6 in initial glioblastoma is not associated with patient survival. ..
  51. Talseth Palmer B, Scott R, Vasen H, Wijnen J. 8q23.3 and 11q23.1 as modifying loci influencing the risk for CRC in Lynch syndrome. Eur J Hum Genet. 2012;20:487-8; author reply 488 pubmed publisher
  52. Stoffel E, Eng C. Exome sequencing in familial colorectal cancer: searching for needles in haystacks. Gastroenterology. 2014;147:554-6 pubmed publisher
  53. Poulos R, Olivier J, Wong J. The interaction between cytosine methylation and processes of DNA replication and repair shape the mutational landscape of cancer genomes. Nucleic Acids Res. 2017;45:7786-7795 pubmed publisher
    ..Our findings reveal links between methylation and common mutation and repair processes, with these mechanisms defining a key part of the mutational landscape of cancer genomes. ..