The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

MSH2  -  mutS homolog 2

Homo sapiens

Synonyms: COCA1, DNA mismatch repair protein Msh2, FCC1, HNPCC, HNPCC1, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of MSH2


Psychiatry related information on MSH2


High impact information on MSH2

  • We investigated a possible role of the mismatch-repair gene MLH3 in hereditary nonpolyposis colorectal cancer by scanning for mutations in 39 HNPCC families and in 288 patients suspected of having HNPCC [7].
  • We identified ten different germline MLH3 variants, one frameshift and nine missense mutations, in 12 patients suspected of HNPCC [7].
  • These different mutator phenotypes provide an explanation for the observation that MSH2 mutations are common in HNPCC families, whereas mutations in MSH3 and MSH6 are rare [8].
  • Involvement of nucleotide-excision repair in msh2 pms1-independent mismatch repair [9].
  • RESULTS: Mutations of MSH2 or MLH1 were found in 47 of the 184 kindreds (26 percent) [1].

Chemical compound and disease context of MSH2


Biological context of MSH2


Anatomical context of MSH2


Associations of MSH2 with chemical compounds

  • 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 [24].
  • Tolerance of human MSH2+/- lymphoblastoid cells to the methylating agent temozolomide [25].
  • MSH2-/- tumors were significantly less responsive to cisplatin than MSH2+/+ tumors, whereas there was no difference in sensitivity to oxaliplatin [23].
  • Consistent with our recent publication, coadministration of IdUrd and a chemical inhibitor of BER, methoxyamine (MX), also increases the extent of MSH2 nuclear colocalization with IdUrd [21].
  • We have previously demonstrated that both the MLH1 and MSH2 status impact the DNA levels of the halogenated thymidine (dThd) analogues iododeoxyuridine (IdUrd) and bromodeoxyuridine (BrdUrd), and thereby radiosensitization induced by these analogues, indirectly implicating both mismatch repair (MMR) proteins in the removal of these bases from DNA [21].

Physical interactions of MSH2

  • As a rule, MSH2 is primarily complexed with MSH6 [26].
  • The EXO1 gene was identified in Saccharomyces cerevisiae as a gene encoding an exonuclease that interacts with MSH2 and functions in mismatch repair and genetic recombination [27].
  • Both the number of RAD51 foci and the amount of the BLM-p53-RAD51 complex are increased in hMSH2- or hMSH6-deficient cells [28].
  • Previous biochemical and physical studies have shown that hMSH2 forms specific mispair binding complexes with hMSH3 and hMSH6 [29].
  • Finally, both Chk1 and Chk2 interact with the MMR protein MSH2, and this interaction is enhanced after MNNG exposure, supporting the notion that the MMR system functions as a molecular scaffold at the sites of DNA damage that facilitates activation of these kinases [30].

Regulatory relationships of MSH2


Other interactions of MSH2

  • In contrast, in cells that overexpress MSH3, the available MSH2 protein is sequestered predominantly into MutSbeta [26].
  • By Western blotting analysis, we found cell lines that are deficient or decreased in the amount of MSH6, or PMS2, or MSH2 proteins [36].
  • In order to further support this hypothesis, we have extended the analysis of the BRAF gene to a different subset of HNPCC families without germline mutations in MLH1 and MSH2 [37].
  • We further demonstrate that the heterodimeric partner of c-MYC, MAX, interacts with a different MMR protein, MSH2, both in vitro and in vivo [38].

Analytical, diagnostic and therapeutic context of MSH2

  • METHODS: We performed Southern blot analysis in 112 patients from MLH1-, MSH2-, and MSH6-negative HNPCC-like families [16].
  • We investigated 100 unselected GCTs and 11 clinically defined chemotherapy-resistant GCTs for MSI using 8 mono- or dinucleotide markers and the presence of the mismatch repair factors MLH1, MSH2, and MSH6 by immunohistochemistry [39].
  • The simplicity and rapidity of their detection, using fluorescent multiplex PCR, led us to recommend to begin the molecular analysis in HNPCC by screening for MSH2 rearrangements [40].
  • Mutation analysis of the MLH1, MSH2, and MSH6 genes was performed (denaturing gradient gel electrophoresis and sequence analysis to detect small mutations and multiplex ligation-dependent probe amplification to detect large deletions or duplications) [41].
  • High-performance liquid chromatography analysis of IdUrd and BrdUrd levels in DNA suggests that this differential cytotoxicity may be due to lower analogue levels in MSH2+ murine and human tumor cells [3].


  1. Clinical findings with implications for genetic testing in families with clustering of colorectal cancer. Wijnen, J.T., Vasen, H.F., Khan, P.M., Zwinderman, A.H., van der Klift, H., Mulder, A., Tops, C., Møller, P., Fodde, R. N. Engl. J. Med. (1998) [Pubmed]
  2. HIF-1alpha induces genetic instability by transcriptionally downregulating MutSalpha expression. Koshiji, M., To, K.K., Hammer, S., Kumamoto, K., Harris, A.L., Modrich, P., Huang, L.E. Mol. Cell (2005) [Pubmed]
  3. Selective radiosensitization of drug-resistant MutS homologue-2 (MSH2) mismatch repair-deficient cells by halogenated thymidine (dThd) analogues: Msh2 mediates dThd analogue DNA levels and the differential cytotoxicity and cell cycle effects of the dThd analogues and 6-thioguanine. Berry, S.E., Davis, T.W., Schupp, J.E., Hwang, H.S., de Wind, N., Kinsella, T.J. Cancer Res. (2000) [Pubmed]
  4. Lack of MSH2 and MSH6 characterizes endometrial but not colon carcinomas in hereditary nonpolyposis colorectal cancer. Schweizer, P., Moisio, A.L., Kuismanen, S.A., Truninger, K., Vierumäki, R., Salovaara, R., Arola, J., Butzow, R., Jiricny, J., Peltomäki, P., Nyström-Lahti, M. Cancer Res. (2001) [Pubmed]
  5. Single-amplicon MSH2 A636P mutation testing in Ashkenazi Jewish patients with colorectal cancer: role in presurgical management. Guillem, J.G., Glogowski, E., Moore, H.G., Nafa, K., Markowitz, A.J., Shia, J., Offit, K., Ellis, N.A. Ann. Surg. (2007) [Pubmed]
  6. Genetic counseling in hereditary nonpolyposis colorectal cancer: an extended family with MSH2 mutation. Lynch, H.T., Lemon, S., Smyrk, T., Franklin, B., Karr, B., Lynch, J., Slominski-Caster, S., Murphy, P., Connolly, C. Am. J. Gastroenterol. (1996) [Pubmed]
  7. A role for MLH3 in hereditary nonpolyposis colorectal cancer. Wu, Y., Berends, M.J., Sijmons, R.H., Mensink, R.G., Verlind, E., Kooi, K.A., van der Sluis, T., Kempinga, C., van dDer Zee, A.G., Hollema, H., Buys, C.H., Kleibeuker, J.H., Hofstra, R.M. Nat. Genet. (2001) [Pubmed]
  8. Novel dominant mutations in Saccharomyces cerevisiae MSH6. Das Gupta, R., Kolodner, R.D. Nat. Genet. (2000) [Pubmed]
  9. Involvement of nucleotide-excision repair in msh2 pms1-independent mismatch repair. Fleck, O., Lehmann, E., Schär, P., Kohli, J. Nat. Genet. (1999) [Pubmed]
  10. Brostallicin (PNU-166196)--a new DNA minor groove binder that retains sensitivity in DNA mismatch repair-deficient tumour cells. Fedier, A., Fowst, C., Tursi, J., Geroni, C., Haller, U., Marchini, S., Fink, D. Br. J. Cancer (2003) [Pubmed]
  11. Induction of two DNA mismatch repair proteins, MSH2 and MSH6, in differentiated human neuroblastoma SH-SY5Y cells exposed to doxorubicin. Belloni, M., Uberti, D., Rizzini, C., Jiricny, J., Memo, M. J. Neurochem. (1999) [Pubmed]
  12. MSH2 codon 322 Gly to Asp seems not to confer an increased risk for colorectal cancer susceptibility. Liu, T., Stathopoulos, P., Lindblom, P., Rubio, C., Wasteson Arver, B., Iselius, L., Holmberg, E., Grönberg, H., Lindblom, A. Eur. J. Cancer (1998) [Pubmed]
  13. Aspirin suppresses the mutator phenotype associated with hereditary nonpolyposis colorectal cancer by genetic selection. Rüschoff, J., Wallinger, S., Dietmaier, W., Bocker, T., Brockhoff, G., Hofstädter, F., Fishel, R. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  14. Expression of DNA repair proteins hMSH2, hMSH6, hMLH1, O6-methylguanine-DNA methyltransferase and N-methylpurine-DNA glycosylase in melanoma cells with acquired drug resistance. Lage, H., Christmann, M., Kern, M.A., Dietel, M., Pick, M., Kaina, B., Schadendorf, D. Int. J. Cancer (1999) [Pubmed]
  15. Immunohistochemical analysis reveals high frequency of PMS2 defects in colorectal cancer. Truninger, K., Menigatti, M., Luz, J., Russell, A., Haider, R., Gebbers, J.O., Bannwart, F., Yurtsever, H., Neuweiler, J., Riehle, H.M., Cattaruzza, M.S., Heinimann, K., Schär, P., Jiricny, J., Marra, G. Gastroenterology (2005) [Pubmed]
  16. Heterozygous mutations in PMS2 cause hereditary nonpolyposis colorectal carcinoma (Lynch syndrome). Hendriks, Y.M., Jagmohan-Changur, S., van der Klift, H.M., Morreau, H., van Puijenbroek, M., Tops, C., van Os, T., Wagner, A., Ausems, M.G., Gomez, E., Breuning, M.H., Bröcker-Vriends, A.H., Vasen, H.F., Wijnen, J.T. Gastroenterology (2006) [Pubmed]
  17. Penetrance and expressivity of MSH6 germline mutations in seven kindreds not ascertained by family history. Buttin, B.M., Powell, M.A., Mutch, D.G., Babb, S.A., Huettner, P.C., Edmonston, T.B., Herzog, T.J., Rader, J.S., Gibb, R.K., Whelan, A.J., Goodfellow, P.J. Am. J. Hum. Genet. (2004) [Pubmed]
  18. Molecular analysis of hereditary nonpolyposis colorectal cancer in the United States: high mutation detection rate among clinically selected families and characterization of an American founder genomic deletion of the MSH2 gene. Wagner, A., Barrows, A., Wijnen, J.T., van der Klift, H., Franken, P.F., Verkuijlen, P., Nakagawa, H., Geugien, M., Jaghmohan-Changur, S., Breukel, C., Meijers-Heijboer, H., Morreau, H., van Puijenbroek, M., Burn, J., Coronel, S., Kinarski, Y., Okimoto, R., Watson, P., Lynch, J.F., de la Chapelle, A., Lynch, H.T., Fodde, R. Am. J. Hum. Genet. (2003) [Pubmed]
  19. Mismatch repair genes on chromosomes 2p and 3p account for a major share of hereditary nonpolyposis colorectal cancer families evaluable by linkage. Nyström-Lahti, M., Parsons, R., Sistonen, P., Pylkkänen, L., Aaltonen, L.A., Leach, F.S., Hamilton, S.R., Watson, P., Bronson, E., Fusaro, R. Am. J. Hum. Genet. (1994) [Pubmed]
  20. Efficient repair of A/C mismatches in mouse cells deficient in long-patch mismatch repair. Oda, S., Humbert, O., Fiumicino, S., Bignami, M., Karran, P. EMBO J. (2000) [Pubmed]
  21. Role of MutSalpha in the recognition of iododeoxyuridine in DNA. Berry, S.E., Loh, T., Yan, T., Kinsella, T.J. Cancer Res. (2003) [Pubmed]
  22. MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: a study of hereditary nonpolyposis colorectal cancer families. Vasen, H.F., Stormorken, A., Menko, F.H., Nagengast, F.M., Kleibeuker, J.H., Griffioen, G., Taal, B.G., Moller, P., Wijnen, J.T. J. Clin. Oncol. (2001) [Pubmed]
  23. In vitro and in vivo resistance to cisplatin in cells that have lost DNA mismatch repair. Fink, D., Zheng, H., Nebel, S., Norris, P.S., Aebi, S., Lin, T.P., Nehmé, A., Christen, R.D., Haas, M., MacLeod, C.L., Howell, S.B. Cancer Res. (1997) [Pubmed]
  24. MSH2 and ATR form a signaling module and regulate two branches of the damage response to DNA methylation. Wang, Y., Qin, J. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  25. Tolerance of human MSH2+/- lymphoblastoid cells to the methylating agent temozolomide. Marra, G., D'Atri, S., Corti, C., Bonmassar, L., Cattaruzza, M.S., Schweizer, P., Heinimann, K., Bartosova, Z., Nyström-Lahti, M., Jiricny, J. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  26. Mismatch repair deficiency associated with overexpression of the MSH3 gene. Marra, G., Iaccarino, I., Lettieri, T., Roscilli, G., Delmastro, P., Jiricny, J. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  27. Identification of a human gene encoding a homologue of Saccharomyces cerevisiae EXO1, an exonuclease implicated in mismatch repair and recombination. Tishkoff, D.X., Amin, N.S., Viars, C.S., Arden, K.C., Kolodner, R.D. Cancer Res. (1998) [Pubmed]
  28. The mismatch DNA repair heterodimer, hMSH2/6, regulates BLM helicase. Yang, Q., Zhang, R., Wang, X.W., Linke, S.P., Sengupta, S., Hickson, I.D., Pedrazzi, G., Perrera, C., Stagljar, I., Littman, S.J., Modrich, P., Harris, C.C. Oncogene (2004) [Pubmed]
  29. Interactions of human hMSH2 with hMSH3 and hMSH2 with hMSH6: examination of mutations found in hereditary nonpolyposis colorectal cancer. Guerrette, S., Wilson, T., Gradia, S., Fishel, R. Mol. Cell. Biol. (1998) [Pubmed]
  30. Methylator-induced, mismatch repair-dependent G2 arrest is activated through Chk1 and Chk2. Adamson, A.W., Beardsley, D.I., Kim, W.J., Gao, Y., Baskaran, R., Brown, K.D. Mol. Biol. Cell (2005) [Pubmed]
  31. Loss of MSH3 protein expression is frequent in MLH1-deficient colorectal cancer and is associated with disease progression. Plaschke, J., Krüger, S., Jeske, B., Theissig, F., Kreuz, F.R., Pistorius, S., Saeger, H.D., Iaccarino, I., Marra, G., Schackert, H.K. Cancer Res. (2004) [Pubmed]
  32. Mismatch repair gene expression and genetic instability in testicular germ cell tumor. Velasco, A., Riquelme, E., Schultz, M., Wistuba, I.I., Villarroel, L., Pizarro, J., Berlin, A., Ittmann, M., Koh, M.S., Leach, F.S. Cancer Biol. Ther. (2004) [Pubmed]
  33. p53 and c-Jun functionally synergize in the regulation of the DNA repair gene hMSH2 in response to UV. Scherer, S.J., Maier, S.M., Seifert, M., Hanselmann, R.G., Zang, K.D., Muller-Hermelink, H.K., Angel, P., Welter, C., Schartl, M. J. Biol. Chem. (2000) [Pubmed]
  34. Bcl2 Impedes DNA Mismatch Repair by Directly Regulating the hMSH2-hMSH6 Heterodimeric Complex. Hou, Y., Gao, F., Wang, Q., Zhao, J., Flagg, T., Zhang, Y., Deng, X. J. Biol. Chem. (2007) [Pubmed]
  35. Expression of the DNA mismatch repair proteins hMLH1 and hPMS2 in normal human tissues. Fink, D., Nebel, S., Aebi, S., Zheng, H., Kim, H.K., Christen, R.D., Howell, S.B. Br. J. Cancer (1997) [Pubmed]
  36. Highly elevated ultraviolet-induced mutation frequency in isolated Chinese hamster cell lines defective in nucleotide excision repair and mismatch repair proteins. Nara, K., Nagashima, F., Yasui, A. Cancer Res. (2001) [Pubmed]
  37. BRAF-V600E is not involved in the colorectal tumorigenesis of HNPCC in patients with functional MLH1 and MSH2 genes. Domingo, E., Niessen, R.C., Oliveira, C., Alhopuro, P., Moutinho, C., Espín, E., Armengol, M., Sijmons, R.H., Kleibeuker, J.H., Seruca, R., Aaltonen, L.A., Imai, K., Yamamoto, H., Schwartz, S., Hofstra, R.M. Oncogene (2005) [Pubmed]
  38. Interactions of the DNA mismatch repair proteins MLH1 and MSH2 with c-MYC and MAX. Mac Partlin, M., Homer, E., Robinson, H., McCormick, C.J., Crouch, D.H., Durant, S.T., Matheson, E.C., Hall, A.G., Gillespie, D.A., Brown, R. Oncogene (2003) [Pubmed]
  39. Microsatellite instability of germ cell tumors is associated with resistance to systemic treatment. Mayer, F., Gillis, A.J., Dinjens, W., Oosterhuis, J.W., Bokemeyer, C., Looijenga, L.H. Cancer Res. (2002) [Pubmed]
  40. MSH2 in contrast to MLH1 and MSH6 is frequently inactivated by exonic and promoter rearrangements in hereditary nonpolyposis colorectal cancer. Charbonnier, F., Olschwang, S., Wang, Q., Boisson, C., Martin, C., Buisine, M.P., Puisieux, A., Frebourg, T. Cancer Res. (2002) [Pubmed]
  41. Toward new strategies to select young endometrial cancer patients for mismatch repair gene mutation analysis. Berends, M.J., Wu, Y., Sijmons, R.H., van der Sluis, T., Ek, W.B., Ligtenberg, M.J., Arts, N.J., ten Hoor, K.A., Kleibeuker, J.H., de Vries, E.G., Mourits, M.J., Hollema, H., Buys, C.H., Hofstra, R.M., van der Zee, A.G. J. Clin. Oncol. (2003) [Pubmed]
WikiGenes - Universities