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

MSH3  -  mismatch repair protein MSH3

Saccharomyces cerevisiae S288c

Synonyms: DNA mismatch repair protein MSH3, MBP, Mismatch-binding protein, MutS protein homolog 3, YCR092C, ...
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 MSH3


High impact information on MSH3

  • In yeast, mutations in several genes, including RTH and MSH3, cause microsatellite instability [1].
  • Introducing chromosome 5, encoding the MSH3 gene, into the mutant cell line increased the stability of some but not all microsatellites [1].
  • Together the data suggest that the MSH3 gene encodes a product that functions in repair of some but not all pre-mutational intermediates, its mutation in tumours can result in genomic instability and, as in yeast, MSH3 and MSH6 are partially redundant for mismatch repair [1].
  • Redundancy of Saccharomyces cerevisiae MSH3 and MSH6 in MSH2-dependent mismatch repair [5].
  • These findings argue that Msh2p-Msh3p associates with intermediates early in DSBR to participate in the rejection of homeologous pairing and to stabilize nonhomologous tails for cleavage by Rad1p-Rad10p endonuclease [6].

Biological context of MSH3

  • In addition to their role in mismatch repair (MMR), the MSH2 and MSH3 gene products are required to remove 3' nonhomologous DNA tails during genetic recombination [7].
  • Interestingly, MSH3 (and thus MutSbeta) is missing in some genomes, as for example in Drosophila, or is present as in Schizosaccharomyces pombe but appears to play no role in MMR [8].
  • In contrast, transcription of the MSH1, MSH3 and MLH1 genes was not regulated during the cell cycle [9].
  • Yeast Msh2p forms complexes with Msh3p and Msh6p to repair DNA mispairs that arise during DNA replication [7].
  • We find that a mutation in the yeast gene MSH3 that does not substantially affect the rate of spontaneous mutations at several loci increases microsatellite instability about 40-fold, preferentially causing deletions [10].

Anatomical context of MSH3

  • In contrast, expression of Msh3 was at its highest level in pachytene spermatocytes [11].
  • To determine the role of MSH3 in mammalian mismatch repair, we employed MSH3-deficient Chinese hamster ovary (CHO) cell lines [12].
  • F19 was either expressed as a fusion with the maltose binding protein (MBP) or directly addressed to the periplasm by fusing it with the MBP signal peptide [13].
  • CONCLUSION: We isolated an MBP from the pancreas and identified it as pancreatic elastase [4].
  • Inhibition of phagocytosis of the yeast also resulted from pretreatment of either the macrophages or the yeasts with MBP followed by washing [14].

Associations of MSH3 with chemical compounds

  • Yeast strains containing alanine substitutions in the PCNA binding motif of Msh6 or Msh3 had elevated mutation rates, indicating that these interactions are important for genome stability [15].
  • In one orientation of the homeologous gene pair, msh2 or msh3 mutations resulted in 17- and 9.6-fold elevations in recombination and the msh2 msh3 double mutant exhibited an 43-fold increase, implying that each MSH gene can function independently in trans to prevent homeologous recombination [16].
  • The human mannose-binding protein (MBP) is a multimeric serum protein that is divided into three domains: a cysteine-rich NH2-terminal domain that stabilizes the alpha-helix of the second collagen-like domain, and a third COOH-terminal carbohydrate binding region [17].
  • The activation by serum MBP was inhibited effectively by the presence of haptenic sugars and dependent absolutely upon the presence of C4, indicating that the activation is initiated by the sugar binding activity of MBP and proceeds through the classical pathway [2].
  • Preincubation of yeasts with rabbit mannose-binding protein (MBP) resulted in dose-related enhancement of TNF-alpha secretion, through a Ca++-dependent pathway inhibited by D-mannose [18].

Other interactions of MSH3


Analytical, diagnostic and therapeutic context of MSH3

  • The median MBP level of ten children previously shown to have the functional opsonic defect was 4.9 micrograms/l (range 2.5-35.0 micrograms/l) compared with 143 micrograms/l (range 2.5-880 micrograms/l) for a paediatric control group [22].
  • We also demonstrate that Kcc4 associates with septin proteins in vitro and in vivo by two-hybrid analysis, GST pull-down experiments, immunoprecipitation, and analysis of direct association with affinity-purified GST-Kcc4 and MBP-Septin proteins [23].
  • In this publication we describe that maltose binding protein (MBP) fused to the C-terminus of the plant photoreceptor phytochrome B allows purification of the fusion protein via amylose affinity chromatography [24].


  1. Mutation of MSH3 in endometrial cancer and evidence for its functional role in heteroduplex repair. Risinger, J.I., Umar, A., Boyd, J., Berchuck, A., Kunkel, T.A., Barrett, J.C. Nat. Genet. (1996) [Pubmed]
  2. Serum lectin with known structure activates complement through the classical pathway. Ikeda, K., Sannoh, T., Kawasaki, N., Kawasaki, T., Yamashina, I. J. Biol. Chem. (1987) [Pubmed]
  3. ATP hydrolysis activity of the DEAD box protein Rok1p is required for in vivo ROK1 function. Oh, J.Y., Kim, J. Nucleic Acids Res. (1999) [Pubmed]
  4. Pancreatic elastase is proven to be a mannose-binding protein--implications for the systemic response to pancreatitis. Zhang, H., Patel, S.A., Kandil, E., Mueller, C.M., Lin, Y.Y., Zenilman, M.E. Surgery (2003) [Pubmed]
  5. Redundancy of Saccharomyces cerevisiae MSH3 and MSH6 in MSH2-dependent mismatch repair. Marsischky, G.T., Filosi, N., Kane, M.F., Kolodner, R. Genes Dev. (1996) [Pubmed]
  6. The Saccharomyces cerevisiae Msh2 mismatch repair protein localizes to recombination intermediates in vivo. Evans, E., Sugawara, N., Haber, J.E., Alani, E. Mol. Cell (2000) [Pubmed]
  7. Separation-of-function mutations in Saccharomyces cerevisiae MSH2 that confer mismatch repair defects but do not affect nonhomologous-tail removal during recombination. Studamire, B., Price, G., Sugawara, N., Haber, J.E., Alani, E. Mol. Cell. Biol. (1999) [Pubmed]
  8. DNA mismatch repair and mutation avoidance pathways. Marti, T.M., Kunz, C., Fleck, O. J. Cell. Physiol. (2002) [Pubmed]
  9. Transcription of mutS and mutL-homologous genes in Saccharomyces cerevisiae during the cell cycle. Kramer, W., Fartmann, B., Ringbeck, E.C. Mol. Gen. Genet. (1996) [Pubmed]
  10. Mutations in the MSH3 gene preferentially lead to deletions within tracts of simple repetitive DNA in Saccharomyces cerevisiae. Strand, M., Earley, M.C., Crouse, G.F., Petes, T.D. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  11. Expression of deoxyribonucleic acid repair enzymes during spermatogenesis in mice. Richardson, L.L., Pedigo, C., Ann Handel, M. Biol. Reprod. (2000) [Pubmed]
  12. MSH3 deficiency is not sufficient for a mutator phenotype in Chinese hamster ovary cells. Hinz, J.M., Meuth, M. Carcinogenesis (1999) [Pubmed]
  13. Assistance of maltose binding protein to the in vivo folding of the disulfide-rich C-terminal fragment from Plasmodium falciparum merozoite surface protein 1 expressed in Escherichia coli. Planson, A.G., Guijarro, J.I., Goldberg, M.E., Chaffotte, A.F. Biochemistry (2003) [Pubmed]
  14. The effect of a mannose binding protein on macrophage interactions with Candida albicans. Kitz, D.J., Stahl, P.D., Little, J.R. Cell. Mol. Biol. (1992) [Pubmed]
  15. Functional interaction of proliferating cell nuclear antigen with MSH2-MSH6 and MSH2-MSH3 complexes. Clark, A.B., Valle, F., Drotschmann, K., Gary, R.K., Kunkel, T.A. J. Biol. Chem. (2000) [Pubmed]
  16. Mismatch correction acts as a barrier to homeologous recombination in Saccharomyces cerevisiae. Selva, E.M., New, L., Crouse, G.F., Lahue, R.S. Genetics (1995) [Pubmed]
  17. The human mannose-binding protein functions as an opsonin. Kuhlman, M., Joiner, K., Ezekowitz, R.A. J. Exp. Med. (1989) [Pubmed]
  18. Serum-mediated enhancement of TNF-alpha release by human monocytes stimulated with the yeast form of Candida albicans. Ghezzi, M.C., Raponi, G., Angeletti, S., Mancini, C. J. Infect. Dis. (1998) [Pubmed]
  19. The prevention of repeat-associated deletions in Saccharomyces cerevisiae by mismatch repair depends on size and origin of deletions. Tran, H.T., Gordenin, D.A., Resnick, M.A. Genetics (1996) [Pubmed]
  20. The Saccharomyces cerevisiae MLH3 gene functions in MSH3-dependent suppression of frameshift mutations. Flores-Rozas, H., Kolodner, R.D. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  21. The effects of mismatch repair and RAD1 genes on interchromosomal crossover recombination in Saccharomyces cerevisiae. Nicholson, A., Fabbri, R.M., Reeves, J.W., Crouse, G.F. Genetics (2006) [Pubmed]
  22. Association of low levels of mannan-binding protein with a common defect of opsonisation. Super, M., Thiel, S., Lu, J., Levinsky, R.J., Turner, M.W. Lancet (1989) [Pubmed]
  23. Kcc4 associates with septin proteins of Saccharomyces cerevisiae. Okuzaki, D., Nojima, H. FEBS Lett. (2001) [Pubmed]
  24. Protein purification with C-terminal fusion of maltose binding protein. Hennig, L., Schäfer, E. Protein Expr. Purif. (1998) [Pubmed]
WikiGenes - Universities