Gene Symbol: MSH6
Description: mutS homolog 6
Alias: GTBP, GTMBP, HNPCC5, HSAP, p160, DNA mismatch repair protein Msh6, G/T mismatch-binding protein, mutS protein homolog 6, mutS-alpha 160 kDa subunit, sperm-associated protein
Species: human
Products:     MSH6

Top Publications

  1. Shia J, Klimstra D, Nafa K, Offit K, Guillem J, Markowitz A, et al. Value of immunohistochemical detection of DNA mismatch repair proteins in predicting germline mutation in hereditary colorectal neoplasms. Am J Surg Pathol. 2005;29:96-104 pubmed
    ..of IHC versus that of microsatellite instability (MSI) testing in predicting mutation status of the MLH1, MSH2, and MSH6 genes in colorectal carcinomas and adenomas, and explored the frequency and significance of immunohistochemical ..
  2. Roncari B, Pedroni M, Maffei S, Di Gregorio C, Ponti G, Scarselli A, et al. Frequency of constitutional MSH6 mutations in a consecutive series of families with clinical suspicion of HNPCC. Clin Genet. 2007;72:230-7 pubmed
    ..In a lower fraction of cases, another gene of the mismatch repair (MMR) machinery, MSH6, may be responsible...
  3. Barrow E, Alduaij W, Robinson L, Shenton A, Clancy T, Lalloo F, et al. Colorectal cancer in HNPCC: cumulative lifetime incidence, survival and tumour distribution. A report of 121 families with proven mutations. Clin Genet. 2008;74:233-42 pubmed publisher
    ..Current colonoscopic screening guidelines are appropriate...
  4. Kolodner R, Tytell J, Schmeits J, Kane M, Gupta R, Weger J, et al. Germ-line msh6 mutations in colorectal cancer families. Cancer Res. 1999;59:5068-74 pubmed
    ..We examined the frequency of germ-line msh6 mutations in a population-based series of 140 colorectal cancer patients, including 45 sporadic cases, 91 familial ..
  5. Etzler J, Peyrl A, Zatkova A, Schildhaus H, Ficek A, Merkelbach Bruse S, et al. RNA-based mutation analysis identifies an unusual MSH6 splicing defect and circumvents PMS2 pseudogene interference. Hum Mutat. 2008;29:299-305 pubmed
    Heterozygous germline mutations in one of the mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2 cause hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome, a dominantly inherited cancer susceptibility syndrome...
  6. Zlatanou A, Despras E, Braz Petta T, Boubakour Azzouz I, Pouvelle C, Stewart G, et al. The hMsh2-hMsh6 complex acts in concert with monoubiquitinated PCNA and Pol ? in response to oxidative DNA damage in human cells. Mol Cell. 2011;43:649-62 pubmed publisher
  7. van der Post R, Kiemeney L, Ligtenberg M, Witjes J, Hulsbergen van de Kaa C, Bodmer D, et al. Risk of urothelial bladder cancer in Lynch syndrome is increased, in particular among MSH2 mutation carriers. J Med Genet. 2010;47:464-70 pubmed publisher
    ..The aim of the present study was to establish whether carriers of mutations in mismatch repair genes MLH1, MSH2 or MSH6 are at increased risk of urinary bladder cancer...
  8. Drummond J, Li G, Longley M, Modrich P. Isolation of an hMSH2-p160 heterodimer that restores DNA mismatch repair to tumor cells. Science. 1995;268:1909-12 pubmed
  9. You J, Buhard O, Ligtenberg M, Kets C, Niessen R, Hofstra R, et al. Tumours with loss of MSH6 expression are MSI-H when screened with a pentaplex of five mononucleotide repeats. Br J Cancer. 2010;103:1840-5 pubmed publisher
    ..are characterised by alterations in one of the four major proteins of the mismatch repair (MMR) system (MLH1, MSH2, MSH6 or PMS2) that renders them MMR deficient, whereas MSI-L and MSS tumours are generally MMR proficient...

More Information


  1. Schöpf B, Bregenhorn S, Quivy J, Kadyrov F, Almouzni G, Jiricny J. Interplay between mismatch repair and chromatin assembly. Proc Natl Acad Sci U S A. 2012;109:1895-900 pubmed publisher
    ..the processivity factor of replicative DNA polymerases, which is loaded at DNA termini and which interacts with the MSH6 subunit of the mismatch recognition factor MutS?, as well as with CAF-1...
  2. Dzantiev L, Constantin N, Genschel J, Iyer R, Burgers P, Modrich P. A defined human system that supports bidirectional mismatch-provoked excision. Mol Cell. 2004;15:31-41 pubmed
    ..By contrast, RFC and PCNA have only a limited effect on 5' to 3' excision directed by a 5' strand break. ..
  3. Risinger J, Umar A, Boyd J, Berchuck A, Kunkel T, Barrett J. Mutation of MSH3 in endometrial cancer and evidence for its functional role in heteroduplex repair. Nat Genet. 1996;14:102-5 pubmed
    ..A subsequent search revealed a second gene mutation in HHUA cells, a missense mutation in the MSH6 gene...
  4. Southey M, Jenkins M, Mead L, Whitty J, Trivett M, Tesoriero A, et al. Use of molecular tumor characteristics to prioritize mismatch repair gene testing in early-onset colorectal cancer. J Clin Oncol. 2005;23:6524-32 pubmed
    ..For the 105 available tumors, MLH1, MSH2, MSH6, and PMS2 protein expression using immunohistochemistry (IHC) and MSI were measured...
  5. Li F, Mao G, Tong D, Huang J, Gu L, Yang W, et al. The histone mark H3K36me3 regulates human DNA mismatch repair through its interaction with MutS?. Cell. 2013;153:590-600 pubmed publisher
    ..This work reveals that a histone mark regulates MMR in human cells and explains the long-standing puzzle of MSI-positive cancer cells that lack detectable mutations in known MMR genes. ..
  6. Berends M, Wu Y, Sijmons R, van der Sluis T, Ek W, Ligtenberg M, et al. Toward new strategies to select young endometrial cancer patients for mismatch repair gene mutation analysis. J Clin Oncol. 2003;21:4364-70 pubmed
    ..Mutation analysis of the MLH1, MSH2, and MSH6 genes was performed (denaturing gradient gel electrophoresis and sequence analysis to detect small mutations and ..
  7. Woods M, Hyde A, Curtis F, Stuckless S, Green J, Pollett A, et al. High frequency of hereditary colorectal cancer in Newfoundland likely involves novel susceptibility genes. Clin Cancer Res. 2005;11:6853-61 pubmed
    ..Tumors from probands were tested by immunohistochemistry for deficiencies in MLH1, MSH2, and MSH6 proteins and tested for DNA microsatellite instability...
  8. Niessen R, Berends M, Wu Y, Sijmons R, Hollema H, Ligtenberg M, et al. Identification of mismatch repair gene mutations in young patients with colorectal cancer and in patients with multiple tumours associated with hereditary non-polyposis colorectal cancer. Gut. 2006;55:1781-8 pubmed
    ..years or with CRC and at least one additional HNPCC-associated cancer, germline mutation analysis in MLH1, MSH2 and MSH6 was carried out with denaturing gradient gel electrophoresis and multiplex ligation-dependent probe amplification...
  9. Owen B, H Lang W, McMurray C. The nucleotide binding dynamics of human MSH2-MSH3 are lesion dependent. Nat Struct Mol Biol. 2009;16:550-7 pubmed publisher
    ..that the human DNA mismatch complex MSH2-MSH3 recognizes small loops by a mechanism different from that of MSH2-MSH6 for single-base mismatches. The subunits MSH2 and MSH3 can bind either ADP or ATP with similar affinities...
  10. Stoffel E, Mukherjee B, Raymond V, Tayob N, Kastrinos F, Sparr J, et al. Calculation of risk of colorectal and endometrial cancer among patients with Lynch syndrome. Gastroenterology. 2009;137:1621-7 pubmed publisher
    ..We studied 147 families with mismatch repair gene mutations (55 MLH1, 81 MSH2, and 11 MSH6) identified at 2 US cancer genetics clinics...
  11. Baglietto L, Lindor N, Dowty J, White D, Wagner A, Gomez Garcia E, et al. Risks of Lynch syndrome cancers for MSH6 mutation carriers. J Natl Cancer Inst. 2010;102:193-201 pubmed publisher
    Germline mutations in MSH6 account for 10%-20% of Lynch syndrome colorectal cancers caused by hereditary DNA mismatch repair gene mutations. Because there have been only a few studies of mutation carriers, their cancer risks are uncertain.
  12. Kantelinen J, Kansikas M, Korhonen M, Ollila S, Heinimann K, Kariola R, et al. MutSbeta exceeds MutSalpha in dinucleotide loop repair. Br J Cancer. 2010;102:1068-73 pubmed publisher
    The target substrates of DNA mismatch recognising factors MutSalpha (MSH2+MSH6) and MutSbeta (MSH2+MSH3) have already been widely researched. However, the extent of their functional redundancy and clinical substance remains unclear...
  13. Acharya S, Wilson T, Gradia S, Kane M, Guerrette S, Marsischky G, et al. hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6. Proc Natl Acad Sci U S A. 1996;93:13629-34 pubmed
    ..proteins, similar to protein complexes demonstrated by studies of the Saccharomyces cerevisiae MSH2, MSH3, and MSH6. hMSH2 was also found to form a homomultimer complex, but neither hMSH3 nor hMSH6 appear to interact with ..
  14. Cyr J, Heinen C. Hereditary cancer-associated missense mutations in hMSH6 uncouple ATP hydrolysis from DNA mismatch binding. J Biol Chem. 2008;283:31641-8 pubmed publisher
  15. Barrow E, Robinson L, Alduaij W, Shenton A, Clancy T, Lalloo F, et al. Cumulative lifetime incidence of extracolonic cancers in Lynch syndrome: a report of 121 families with proven mutations. Clin Genet. 2009;75:141-9 pubmed publisher
    ..0003). Gastric cancer risk in those born after 1935 does not justify surveillance. These penetrance estimates have been corrected for ascertainment bias and are appropriate for those referred to a high-risk clinic...
  16. Kastrinos F, Syngal S. Recently identified colon cancer predispositions: MYH and MSH6 mutations. Semin Oncol. 2007;34:418-24 pubmed
    ..Most recently, MYH-associated polyposis (MAP) and an "atypical Lynch syndrome" related to the presence of MSH6 mutations have been linked to an increased risk of CRC...
  17. Lamberti C, Mangold E, Pagenstecher C, Jungck M, Schwering D, Bollmann M, et al. Frequency of hereditary non-polyposis colorectal cancer among unselected patients with colorectal cancer in Germany. Digestion. 2006;74:58-67 pubmed
    ..MSH2 and MLH1 mutations; 19/40 patients with MSI and normal MSH2 or MLH1 expression were screened for mutations in MSH6. Three patients had relevant MMR gene mutations and six variants of unknown functional relevance were detected...
  18. Zhao Y, Hu F, Wang F, Han B, Li D, Li X, et al. Meta-analysis of MSH6 gene mutation frequency in colorectal and endometrial cancers. J Toxicol Environ Health A. 2009;72:690-7 pubmed publisher
    Studies on mutations and mutation frequencies of the MSH6 gene, which mainly focus on new types of mutations in small samples, have been published ever since the first report of MSH6 mutation in two atypical hereditary non-polyposis ..
  19. Giráldez M, Balaguer F, Bujanda L, Cuatrecasas M, Muñoz J, Alonso Espinaco V, et al. MSH6 and MUTYH deficiency is a frequent event in early-onset colorectal cancer. Clin Cancer Res. 2010;16:5402-13 pubmed publisher
    ..MMR) deficiency was determined by microsatellite instability (MSI) analysis, and immunostaining for MLH1, MSH2, MSH6, and PMS2 proteins. Germline MMR mutations were evaluated in all MMR-deficient cases...
  20. Larson E, Duquette M, Cummings W, Streiff R, Maizels N. MutSalpha binds to and promotes synapsis of transcriptionally activated immunoglobulin switch regions. Curr Biol. 2005;15:470-4 pubmed
    ..deaminase, AID, and conserved DNA repair factors, including the mismatch repair heterodimer, MutSalpha (MSH2/MSH6)...
  21. Niessen R, Sijmons R, Ou J, Olthof S, Osinga J, Ligtenberg M, et al. MUTYH and the mismatch repair system: partners in crime?. Hum Genet. 2006;119:206-11 pubmed
    ..5%). In group II five monoallelic germline MUTYH mutations were found (14%), four of them in MSH6 missense mutation carriers (20%)...
  22. Wu Y, Berends M, Mensink R, Kempinga C, Sijmons R, van der Zee A, et al. Association of hereditary nonpolyposis colorectal cancer-related tumors displaying low microsatellite instability with MSH6 germline mutations. Am J Hum Genet. 1999;65:1291-8 pubmed
    ..Correction of base-base mismatches is the major function of MSH6. Since mismatches present with an MSI-low phenotype, we assumed that the phenotype in patients with HNPCC-related ..
  23. Kleczkowska H, Marra G, Lettieri T, Jiricny J. hMSH3 and hMSH6 interact with PCNA and colocalize with it to replication foci. Genes Dev. 2001;15:724-36 pubmed
    ..We postulate that PCNA plays a role in repair initiation by guiding the mismatch repair proteins to free termini in the newly replicated DNA strands. ..
  24. Guerrette S, Wilson T, Gradia S, Fishel R. Interactions of human hMSH2 with hMSH3 and hMSH2 with hMSH6: examination of mutations found in hereditary nonpolyposis colorectal cancer. Mol Cell Biol. 1998;18:6616-23 pubmed
    ..These data support the notion that these HNPCC-associated mutations may affect some other function of the heterodimeric complexes than simply the static interaction of hMSH2 with hMSH3 or hMSH2 with hMSH6. ..
  25. Papadopoulos N, Nicolaides N, Liu B, Parsons R, Lengauer C, Palombo F, et al. Mutations of GTBP in genetically unstable cells. Science. 1995;268:1915-7 pubmed
    ..Here the gene encoding a G/T mismatch-binding protein (GTBP) was localized to within 1 megabase of the related hMSH2 gene on chromosome 2 and was found to be inactivated in ..
  26. Rasmussen L, Rasmussen M, Lee B, Rasmussen A, Wilson D, Nielsen F, et al. Identification of factors interacting with hMSH2 in the fetal liver utilizing the yeast two-hybrid system. In vivo interaction through the C-terminal domains of hEXO1 and hMSH2 and comparative expression analysis. Mutat Res. 2000;460:41-52 pubmed
    ..Northern blot analysis also revealed that hEXO1/HEX1 is highly expressed in several liver cancer cell lines as well as in colon and pancreas adenocarcinomas, but not in the corresponding non-neoplastic tissue. ..
  27. Wijnen J, De Leeuw W, Vasen H, van der Klift H, Møller P, Stormorken A, et al. Familial endometrial cancer in female carriers of MSH6 germline mutations. Nat Genet. 1999;23:142-4 pubmed
  28. Vasen H, Stormorken A, Menko F, Nagengast F, Kleibeuker J, Griffioen G, et al. MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: a study of hereditary nonpolyposis colorectal cancer families. J Clin Oncol. 2001;19:4074-80 pubmed
    ..The disease is caused by mutations in DNA-mismatch-repair (MMR) genes, most frequently in MLH1, MSH2, and MSH6. The aims of the present study were to compare the risk of developing colorectal, endometrial, and other cancers ..
  29. Ramsoekh D, Wagner A, van Leerdam M, Dinjens W, Steyerberg E, Halley D, et al. A high incidence of MSH6 mutations in Amsterdam criteria II-negative families tested in a diagnostic setting. Gut. 2008;57:1539-44 pubmed publisher
    In Lynch syndrome, the clinical phenotype in MSH6 mutation families differs from that in MLH1 and MSH2 families...
  30. Nilbert M, Wikman F, Hansen T, Krarup H, Orntoft T, Nielsen F, et al. Major contribution from recurrent alterations and MSH6 mutations in the Danish Lynch syndrome population. Fam Cancer. 2009;8:75-83 pubmed publisher
    ..The different MMR genes contribute to 40% (MSH2), 29% (MLH1), and 22% (MSH6) of the mutations and the Danish population thus shows a considerably higher frequency of MSH6 mutations than ..
  31. Berends M, Wu Y, Sijmons R, Mensink R, van der Sluis T, Hordijk Hos J, et al. Molecular and clinical characteristics of MSH6 variants: an analysis of 25 index carriers of a germline variant. Am J Hum Genet. 2002;70:26-37 pubmed
    The MSH6 gene is one of the mismatch-repair genes involved in hereditary nonpolyposis colorectal cancer (HNPCC). Three hundred sixteen individuals who were known or suspected to have HNPCC were analyzed for MSH6 germline mutations...
  32. Devlin L, Graham C, Price J, Morrison P. Germline MSH6 mutations are more prevalent in endometrial cancer patient cohorts than hereditary non polyposis colorectal cancer cohorts. Ulster Med J. 2008;77:25-30 pubmed
    To determine and compare the prevalence of MSH6 (a mismatch repair gene) mutations in a cohort of families with Hereditary Non-Polyposis Colorectal Cancer (HNPCC), and in an unselected cohort of endometrial cancer patients (EC)...
  33. Miyaki M, Konishi M, Tanaka K, Kikuchi Yanoshita R, Muraoka M, Yasuno M, et al. Germline mutation of MSH6 as the cause of hereditary nonpolyposis colorectal cancer. Nat Genet. 1997;17:271-2 pubmed
  34. Lagerstedt Robinson K, Liu T, Vandrovcova J, Halvarsson B, Clendenning M, Frebourg T, et al. Lynch syndrome (hereditary nonpolyposis colorectal cancer) diagnostics. J Natl Cancer Inst. 2007;99:291-9 pubmed for patients at high risk for HNPCC were selected for screening to detect mutations in MMR genes MLH1, MSH2, MSH6, and PMS2 based on family history, microsatellite instability (MSI), and immunohistochemical analysis of MMR ..
  35. Goodfellow P, Buttin B, Herzog T, Rader J, Gibb R, Swisher E, et al. Prevalence of defective DNA mismatch repair and MSH6 mutation in an unselected series of endometrial cancers. Proc Natl Acad Sci U S A. 2003;100:5908-13 pubmed
    ..Sporadic endometrial cancers also exhibit MSI, usually associated with methylation of the MLH1 promoter. Germ-line MSH6 mutations, which are rare in HNPCC, have been reported in several families with multiple members affected with ..
  36. Win A, Young J, Lindor N, Tucker K, Ahnen D, Young G, et al. Colorectal and other cancer risks for carriers and noncarriers from families with a DNA mismatch repair gene mutation: a prospective cohort study. J Clin Oncol. 2012;30:958-64 pubmed publisher
    ..prospectively followed a cohort of 446 unaffected carriers of an MMR gene mutation (MLH1, n = 161; MSH2, n = 222; MSH6, n = 47; and PMS2, n = 16) and 1,029 their unaffected relatives who did not carry a mutation every 5 years at ..
  37. Pedrazzi G, Bachrati C, Selak N, Studer I, Petkovic M, Hickson I, et al. The Bloom's syndrome helicase interacts directly with the human DNA mismatch repair protein hMSH6. Biol Chem. 2003;384:1155-64 pubmed
  38. Plaschke J, Kruger S, Pistorius S, Theissig F, Saeger H, Schackert H. Involvement of hMSH6 in the development of hereditary and sporadic colorectal cancer revealed by immunostaining is based on germline mutations, but rarely on somatic inactivation. Int J Cancer. 2002;97:643-8 pubmed
    ..We conclude that the involvement of somatic or epigenetic hMSH6 inactivation in colorectal cancer is rare. ..
  39. Kaur G, Masoud A, Raihan N, Radzi M, Khamizar W, Kam L. Mismatch repair genes expression defects & association with clinicopathological characteristics in colorectal carcinoma. Indian J Med Res. 2011;134:186-92 pubmed
    ..Immunohistochemistry for MLH1, MSH2, MSH6 and PMS2 proteins were performed on paraffin embedded tissue containing carcinoma...
  40. Gradia S, Acharya S, Fishel R. The human mismatch recognition complex hMSH2-hMSH6 functions as a novel molecular switch. Cell. 1997;91:995-1005 pubmed
    ..These results suggest a new model for the function of MutS proteins during mismatch repair in which the switch determines the timing of downstream events. ..
  41. Kariola R, Otway R, Lönnqvist K, Raevaara T, Macrae F, Vos Y, et al. Two mismatch repair gene mutations found in a colon cancer patient--which one is pathogenic?. Hum Genet. 2003;112:105-9 pubmed
    ..Germline mutations in five different mismatch repair (MMR) genes, MSH2, MSH6, MLH1, MLH3, and PMS2 are linked to HNPCC...
  42. Hampel H, Frankel W, Panescu J, Lockman J, Sotamaa K, Fix D, et al. Screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer) among endometrial cancer patients. Cancer Res. 2006;66:7810-7 pubmed
    ..Patients with MSI-positive tumors underwent testing for germ line mutations in MLH1, MSH2, MSH6, and PMS2. Of 543 tumors studied, 118 (21.7%) were MSI positive (98 of 118 MSI high and 20 of 118 MSI low)...
  43. Wagner A, Hendriks Y, Meijers Heijboer E, de Leeuw W, Morreau H, Hofstra R, et al. Atypical HNPCC owing to MSH6 germline mutations: analysis of a large Dutch pedigree. J Med Genet. 2001;38:318-22 pubmed
    ..Recently, mutations in another MMR gene, MSH6 (also known as GTBP), have also been shown to result in HNPCC...
  44. Grindedal E, Møller P, Eeles R, Stormorken A, Bowitz Lothe I, Landrø S, et al. Germ-line mutations in mismatch repair genes associated with prostate cancer. Cancer Epidemiol Biomarkers Prev. 2009;18:2460-7 pubmed publisher
    ..The mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2 are associated with Lynch syndrome where colon and endometrial cancers are the predominant phenotypes...
  45. Ripperger T, Beger C, Rahner N, Sykora K, Bockmeyer C, Lehmann U, et al. Constitutional mismatch repair deficiency and childhood leukemia/lymphoma--report on a novel biallelic MSH6 mutation. Haematologica. 2010;95:841-4 pubmed publisher
    ..We report on a case with constitutional mismatch repair deficiency caused by a novel MSH6 mutation leading to a T-cell lymphoma and colonic adenocarcinoma at six and 13 years of age, respectively...
  46. Ramsoekh D, Wagner A, van Leerdam M, Dooijes D, Tops C, Steyerberg E, et al. Cancer risk in MLH1, MSH2 and MSH6 mutation carriers; different risk profiles may influence clinical management. Hered Cancer Clin Pract. 2009;7:17 pubmed publisher
    ..The aim of the present study was to calculate the cumulative risk of LS related cancers in proven MLH1, MSH2 and MSH6 mutation carriers. The studypopulation consisted out of 67 proven LS families...
  47. Ghosal G, Leung J, Nair B, Fong K, Chen J. Proliferating cell nuclear antigen (PCNA)-binding protein C1orf124 is a regulator of translesion synthesis. J Biol Chem. 2012;287:34225-33 pubmed publisher
    ..Thus, C1orf124 acts at multiple steps in TLS, stabilizes RAD18 and ubiquitinated PCNA at damage sites, and facilitates the switch from replicative to TLS polymerase to bypass DNA lesion. ..
  48. Wang Q, Zhang H, Guerrette S, Chen J, Mazurek A, Wilson T, et al. Adenosine nucleotide modulates the physical interaction between hMSH2 and BRCA1. Oncogene. 2001;20:4640-9 pubmed
    ..The functional interaction between BRCA1 and hMSH2 may provide a partial explanation for the background of gynecological and colorectal cancer in both HNPCC and BRCA1 kindreds, respectively. ..
  49. Wang Y, Cortez D, Yazdi P, Neff N, Elledge S, Qin J. BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures. Genes Dev. 2000;14:927-39 pubmed
    ..This complex includes tumor suppressors and DNA damage repair proteins MSH2, MSH6, MLH1, ATM, BLM, and the RAD50-MRE11-NBS1 protein complex...
  50. Christmann M, Kaina B. Nuclear translocation of mismatch repair proteins MSH2 and MSH6 as a response of cells to alkylating agents. J Biol Chem. 2000;275:36256-62 pubmed DNA, such as N-methyl-N'-nitro-N-nitrosoguanidine and N-methyl-N-nitrosourea, elevates the level of MSH2 and MSH6 and increases GT mismatch binding activity in the nucleus...
  51. Laguri C, Duband Goulet I, Friedrich N, Axt M, Belin P, Callebaut I, et al. Human mismatch repair protein MSH6 contains a PWWP domain that targets double stranded DNA. Biochemistry. 2008;47:6199-207 pubmed publisher
    The eukaryotic mismatch repair (MMR) protein MSH6 exhibits a core region structurally and functionally similar to bacterial MutS...
  52. Plaschke J, Ruschoff J, Schackert H. Genomic rearrangements of hMSH6 contribute to the genetic predisposition in suspected hereditary non-polyposis colorectal cancer syndrome. J Med Genet. 2003;40:597-600 pubmed
  53. Peterlongo P, Nafa K, Lerman G, Glogowski E, Shia J, Ye T, et al. MSH6 germline mutations are rare in colorectal cancer families. Int J Cancer. 2003;107:571-9 pubmed
    Germline mutations in MSH6 can cause HNPCC, which is associated with a tumor phenotype featuring MSI. However, tumors arising in persons with disease-causing mutations of MSH6 may or may not exhibit MSI...
  54. Wang Y, Qin J. MSH2 and ATR form a signaling module and regulate two branches of the damage response to DNA methylation. Proc Natl Acad Sci U S A. 2003;100:15387-92 pubmed
    ..These data support a model in which MSH2 and ATR function upstream to regulate two branches of the response pathway to DNA damage caused by MNNG. ..
  55. Yang Q, Zhang R, Wang X, Linke S, Sengupta S, Hickson I, et al. The mismatch DNA repair heterodimer, hMSH2/6, regulates BLM helicase. Oncogene. 2004;23:3749-56 pubmed
    ..These data suggest that hMSH2/6 formed a complex with BLM-p53-RAD51 in response to the damaged DNA forks during double-stranded break repair. ..
  56. Bonadona V, Bonaïti B, Olschwang S, Grandjouan S, Huiart L, Longy M, et al. Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA. 2011;305:2304-10 pubmed publisher
    ..risks of developing various tumors using a large series of families with mutations of the MLH1, MSH2, and MSH6 genes...
  57. Iyer R, Pohlhaus T, Chen S, Hura G, Dzantiev L, Beese L, et al. The MutSalpha-proliferating cell nuclear antigen interaction in human DNA mismatch repair. J Biol Chem. 2008;283:13310-9 pubmed publisher
  58. Kariola R, Raevaara T, Lönnqvist K, Nystrom Lahti M. Functional analysis of MSH6 mutations linked to kindreds with putative hereditary non-polyposis colorectal cancer syndrome. Hum Mol Genet. 2002;11:1303-10 pubmed
    To date, five mismatch-repair (MMR) genes, MLH1, MSH2, MSH6, MSH3 and PMS2, are known to be involved in human MMR function...