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Gene Review

MSH5  -  MutS family protein MSH5

Saccharomyces cerevisiae S288c

Synonyms: D1542, MutS protein homolog 5, YDL154W
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High impact information on MSH5

  • Absence of either of the meiosis-specific mutS homologs Msh4 or Msh5 results in a similar reduction in crossing-over [1].
  • Diploids lacking the MSH5 gene display decreased levels of spore viability, increased levels of meiosis I chromosome nondisjuction, and decreased levels of reciprocal exchange between, but not within, homologs [2].
  • Here we describe the identification of the human homologue of the Saccharomyces cerevisiae MSH5, which is known to participate in meiotic segregation fidelity and crossing-over [3].
  • A mutation in the MSH5 gene results in alkylation tolerance [4].
  • We further demonstrated that a mutated form of the MSH5 gene, msh5-14, not the msh5delta-null mutation, is responsible for the cellular tolerance to MNNG in XS-14 cells [4].

Biological context of MSH5


Anatomical context of MSH5

  • A large number of mgt1delta, MNNG-tolerant revertants were isolated, among which one cell line, XS-14, has been found to carry a mutated allele of the MSH5 gene [4].
  • Northern blot analysis demonstrated the presence of a 2.9-kb human MSH5 mRNA species in all human tissues tested, but the highest expression was in human testis, an organ containing cells that undergo constant DNA synthesis and meiosis [6].

Regulatory relationships of MSH5


Other interactions of MSH5

  • Mutation of conserved amino acids in the NTP binding and putative helix-turn-helix domains of Msh5p abolish function but are still capable of interaction with Msh4p, suggesting that NTP binding plays a role downstream of hetero-oligomer formation [9].
  • In contrast, MMS4 functions independently of MSH5 in the production of viable spores [10].
  • Exo1p functions in the same pathway as Msh5p for intergenic recombination [11].

Analytical, diagnostic and therapeutic context of MSH5


  1. Mlh1 is unique among mismatch repair proteins in its ability to promote crossing-over during meiosis. Hunter, N., Borts, R.H. Genes Dev. (1997) [Pubmed]
  2. MSH5, a novel MutS homolog, facilitates meiotic reciprocal recombination between homologs in Saccharomyces cerevisiae but not mismatch repair. Hollingsworth, N.M., Ponte, L., Halsey, C. Genes Dev. (1995) [Pubmed]
  3. hMSH5: a human MutS homologue that forms a novel heterodimer with hMSH4 and is expressed during spermatogenesis. Bocker, T., Barusevicius, A., Snowden, T., Rasio, D., Guerrette, S., Robbins, D., Schmidt, C., Burczak, J., Croce, C.M., Copeland, T., Kovatich, A.J., Fishel, R. Cancer Res. (1999) [Pubmed]
  4. A mutation in the MSH5 gene results in alkylation tolerance. Bawa, S., Xiao, W. Cancer Res. (1997) [Pubmed]
  5. Cloning and characterization of the human and Caenorhabditis elegans homologs of the Saccharomyces cerevisiae MSH5 gene. Winand, N.J., Panzer, J.A., Kolodner, R.D. Genomics (1998) [Pubmed]
  6. Cloning, structural characterization, and chromosomal localization of the human orthologue of Saccharomyces cerevisiae MSH5 gene. Her, C., Doggett, N.A. Genomics (1998) [Pubmed]
  7. A single amino acid substitution in MSH5 results in DNA alkylation tolerance. Bawa, S., Xiao, W. Gene (2003) [Pubmed]
  8. Caenorhabditis elegans msh-5 is required for both normal and radiation-induced meiotic crossing over but not for completion of meiosis. Kelly, K.O., Dernburg, A.F., Stanfield, G.M., Villeneuve, A.M. Genetics (2000) [Pubmed]
  9. Conserved properties between functionally distinct MutS homologs in yeast. Pochart, P., Woltering, D., Hollingsworth, N.M. J. Biol. Chem. (1997) [Pubmed]
  10. A role for MMS4 in the processing of recombination intermediates during meiosis in Saccharomyces cerevisiae. de los Santos, T., Loidl, J., Larkin, B., Hollingsworth, N.M. Genetics (2001) [Pubmed]
  11. Decreased meiotic intergenic recombination and increased meiosis I nondisjunction in exo1 mutants of Saccharomyces cerevisiae. Kirkpatrick, D.T., Ferguson, J.R., Petes, T.D., Symington, L.S. Genetics (2000) [Pubmed]
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