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Gene Review

MSH3  -  mutS homolog 3

Homo sapiens

Synonyms: DNA mismatch repair protein Msh3, DUC1, DUG, DUP, Divergent upstream protein, ...
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Disease relevance of MSH3


Psychiatry related information on MSH3

  • The other explicit memory tests and the reaction time test showed no effect with DUP 996 [5].

High impact information on MSH3


Chemical compound and disease context of MSH3


Biological context of MSH3


Anatomical context of MSH3


Associations of MSH3 with chemical compounds

  • DHFR/MSH3 amplification in methotrexate-resistant cells alters the hMutSalpha/hMutSbeta ratio and reduces the efficiency of base-base mismatch repair [18].
  • Because processing certain types of DNA damage by the mismatch repair pathway has also been implicated in tumor sensitivity to agents such as cisplatin, changes in expression at the DHFR/MSH3 locus may have further relevance to the outcome of multi-drug treatment regimens [19].
  • After 5-aza-dC treatment, MSH3 expression was significantly enhanced in TCC and UMUC bladder cancer cells when compared to untreated cells [20].
  • These studies support the idea that hMSH2-hMSH3 functions as an adenosine nucleotide-regulated molecular switch that must be activated by mismatched nucleotides for classical mismatch repair to occur [21].
  • Mismatch repair (MMR) is initiated by MutS family proteins (MSH) that recognize DNA mismatches and recruit downstream repair factors [22].

Physical interactions of MSH3


Enzymatic interactions of MSH3

  • Sixty five percent of the patients deleted at hMLH1 were also deleted at hMSH3 [24].

Other interactions of MSH3


Analytical, diagnostic and therapeutic context of MSH3


  1. 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]
  2. MSH6 and MSH3 are rarely involved in genetic predisposition to nonpolypotic colon cancer. Huang, J., Kuismanen, S.A., Liu, T., Chadwick, R.B., Johnson, C.K., Stevens, M.W., Richards, S.K., Meek, J.E., Gao, X., Wright, F.A., Mecklin, J.P., Järvinen, H.J., Grönberg, H., Bisgaard, M.L., Lindblom, A., Peltomäki, P. Cancer Res. (2001) [Pubmed]
  3. Mismatch repair and microsatellite instability in esophageal cancer cells. Uchida, N., Kumimoto, H., Nishizawa, K., Tokumasu, S., Harada, H., Shimada, Y., Ishizaki, K. Int. J. Cancer (2001) [Pubmed]
  4. Mismatch repair gene expression defects contribute to microsatellite instability in ovarian carcinoma. Geisler, J.P., Goodheart, M.J., Sood, A.K., Holmes, R.J., Hatterman-Zogg, M.A., Buller, R.E. Cancer (2003) [Pubmed]
  5. Linopirdine (DUP 996): cholinergic treatment of older adults using successive and non-successive tests. Börjesson, A., Karlsson, T., Adolfsson, R., Rönnlund, M., Nilsson, L. Neuropsychobiology (1999) [Pubmed]
  6. Mismatch repair in replication fidelity, genetic recombination, and cancer biology. Modrich, P., Lahue, R. Annu. Rev. Biochem. (1996) [Pubmed]
  7. HNPCC-like cancer predisposition in mice through simultaneous loss of Msh3 and Msh6 mismatch-repair protein functions. de Wind, N., Dekker, M., Claij, N., Jansen, L., van Klink, Y., Radman, M., Riggins, G., van der Valk, M., van't Wout, K., te Riele, H. Nat. Genet. (1999) [Pubmed]
  8. Requirement for PCNA in DNA mismatch repair at a step preceding DNA resynthesis. Umar, A., Buermeyer, A.B., Simon, J.A., Thomas, D.C., Clark, A.B., Liskay, R.M., Kunkel, T.A. Cell (1996) [Pubmed]
  9. Mismatch repair gene defects in sporadic colorectal cancers with microsatellite instability. Liu, B., Nicolaides, N.C., Markowitz, S., Willson, J.K., Parsons, R.E., Jen, J., Papadopolous, N., Peltomäki, P., de la Chapelle, A., Hamilton, S.R. Nat. Genet. (1995) [Pubmed]
  10. DNA mismatch repair genes in renal cell carcinoma. Deguchi, M., Shiina, H., Igawa, M., Kaneuchi, M., Nakajima, K., Dahiya, R. J. Urol. (2003) [Pubmed]
  11. Mismatch repair status in the prediction of benefit from adjuvant fluorouracil chemotherapy in colorectal cancer. Jover, R., Zapater, P., Castells, A., Llor, X., Andreu, M., Cubiella, J., Piñol, V., Xicola, R.M., Bujanda, L., Reñé, J.M., Clofent, J., Bessa, X., Morillas, J.D., Nicolás-Pérez, D., Payá, A., Alenda, C. Gut (2006) [Pubmed]
  12. Endometrial and colorectal tumors from patients with hereditary nonpolyposis colon cancer display different patterns of microsatellite instability. Kuismanen, S.A., Moisio, A.L., Schweizer, P., Truninger, K., Salovaara, R., Arola, J., Butzow, R., Jiricny, J., Nyström-Lahti, M., Peltomäki, P. Am. J. Pathol. (2002) [Pubmed]
  13. Common variants in mismatch repair genes and risk of invasive ovarian cancer. Song, H., Ramus, S.J., Quaye, L., Dicioccio, R.A., Tyrer, J., Lomas, E., Shadforth, D., Hogdall, E., Hogdall, C., McGuire, V., Whittemore, A.S., Easton, D.F., Ponder, B.A., Kjaer, S.K., Pharoah, P.D., Gayther, S.A. Carcinogenesis (2006) [Pubmed]
  14. Microsatellite instability and mismatch repair target gene mutations in cell lines and xenografts of prostate cancer. Sun, X., Chen, C., Vessella, R.L., Dong, J.T. Prostate (2006) [Pubmed]
  15. Mutation spectrum of MSH3-deficient HHUA/chr.2 cells reflects in vivo activity of the MSH3 gene product in mismatch repair. Tauchi, H., Komatsu, K., Ishizaki, K., Yatagai, F., Kato, T. Mutat. Res. (2000) [Pubmed]
  16. Mismatch repair gene expression in malignant lymphoproliferative disorders of B-cell origin. Kotoula, V., Hytiroglou, P., Kaloutsi, V., Barbanis, S., Kouidou, S., Papadimitriou, C.S. Leuk. Lymphoma (2002) [Pubmed]
  17. Mismatch repair gene defects contribute to the genetic basis of double primary cancers of the colorectum and endometrium. Millar, A.L., Pal, T., Madlensky, L., Sherman, C., Temple, L., Mitri, A., Cheng, H., Marcus, V., Gallinger, S., Redston, M., Bapat, B., Narod, S. Hum. Mol. Genet. (1999) [Pubmed]
  18. DHFR/MSH3 amplification in methotrexate-resistant cells alters the hMutSalpha/hMutSbeta ratio and reduces the efficiency of base-base mismatch repair. Drummond, J.T., Genschel, J., Wolf, E., Modrich, P. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  19. Genomic amplification of the human DHFR/MSH3 locus remodels mismatch recognition and repair activities. Drummond, J.T. Adv. Enzyme Regul. (1999) [Pubmed]
  20. Inactivation of the hMSH3 mismatch repair gene in bladder cancer. Kawakami, T., Shiina, H., Igawa, M., Deguchi, M., Nakajima, K., Ogishima, T., Tokizane, T., Urakami, S., Enokida, H., Miura, K., Ishii, N., Kane, C.J., Carroll, P.R., Dahiya, R. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  21. Dissociation of mismatch recognition and ATPase activity by hMSH2-hMSH3. Wilson, T., Guerrette, S., Fishel, R. J. Biol. Chem. (1999) [Pubmed]
  22. Detection of high-affinity and sliding clamp modes for MSH2-MSH6 by single-molecule unzipping force analysis. Jiang, J., Bai, L., Surtees, J.A., Gemici, Z., Wang, M.D., Alani, E. Mol. Cell (2005) [Pubmed]
  23. hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6. Acharya, S., Wilson, T., Gradia, S., Kane, M.F., Guerrette, S., Marsischky, G.T., Kolodner, R., Fishel, R. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  24. High resolution deletion mapping reveals frequent allelic losses at the DNA mismatch repair loci hMLH1 and hMSH3 in non-small cell lung cancer. Benachenhou, N., Guiral, S., Gorska-Flipot, I., Labuda, D., Sinnett, D. Int. J. Cancer (1998) [Pubmed]
  25. 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]
  26. Germline and somatic mutation analysis of MLH3 in MSI-positive colorectal cancer. Loukola, A., Vilkki, S., Singh, J., Launonen, V., Aaltonen, L.A. Am. J. Pathol. (2000) [Pubmed]
  27. Functional overlap in mismatch repair by human MSH3 and MSH6. Umar, A., Risinger, J.I., Glaab, W.E., Tindall, K.R., Barrett, J.C., Kunkel, T.A. Genetics (1998) [Pubmed]
  28. Frequent microsatellite instability in primary esophageal carcinoma associated with extraesophageal primary carcinoma. Kubo, N., Yashiro, M., Ohira, M., Hori, T., Fujiwara, I., Hirakawa, K. Int. J. Cancer (2005) [Pubmed]
  29. Mismatch repair in extracts of Werner syndrome cell lines. Bennett, S.E., Umar, A., Oshima, J., Monnat, R.J., Kunkel, T.A. Cancer Res. (1997) [Pubmed]
  30. Analysis of MSH3 in endometrial cancers with defective DNA mismatch repair. Swisher, E.M., Mutch, D.G., Herzog, T.J., Rader, J.S., Kowalski, L.D., Elbendary, A., Goodfellow, P.J. J. Soc. Gynecol. Investig. (1998) [Pubmed]
  31. Microsatellite instability and suppressed DNA repair enzyme expression in rheumatoid arthritis. Lee, S.H., Chang, D.K., Goel, A., Boland, C.R., Bugbee, W., Boyle, D.L., Firestein, G.S. J. Immunol. (2003) [Pubmed]
  32. Mutation of hMSH3 and hMSH6 mismatch repair genes in genetically unstable human colorectal and gastric carcinomas. Yin, J., Kong, D., Wang, S., Zou, T.T., Souza, R.F., Smolinski, K.N., Lynch, P.M., Hamilton, S.R., Sugimura, H., Powell, S.M., Young, J., Abraham, J.M., Meltzer, S.J. Hum. Mutat. (1997) [Pubmed]
  33. DNA mismatch repair enzyme expression in synovial tissue. Simelyte, E., Boyle, D.L., Firestein, G.S. Ann. Rheum. Dis. (2004) [Pubmed]
  34. Tissue microarray analysis of hMSH2 expression predicts outcome in men with prostate cancer. Prtilo, A., Leach, F.S., Markwalder, R., Kappeler, A., Burkhard, F.C., Cecchini, M.G., Studer, U.E., Thalmann, G.N. J. Urol. (2005) [Pubmed]
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