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Gene Review

MSH4  -  MutS family protein MSH4

Saccharomyces cerevisiae S288c

Synonyms: MutS protein homolog 4, YFL003C
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High impact information on MSH4

  • Immunofluorescence experiments demonstrate that the Msh4 protein is localized to discrete sites on pachytene chromosomes [1].
  • RNAi-induced down-regulation of the MSH4 gene resulted in a similar fertility and meiotic phenotype [2].
  • Msh5 mutants are phenotypically similar to mutants in the meiosis-specific gene MSH4 (Ross-Macdonald and Roeder 1994) [3].
  • Double mutant analysis using msh4 msh5 diploids demonstrates that the two genes are in the same epistasis group and therefore are likely to function in a similar process--namely, the facilitation of interhomolog crossovers during meiosis [3].
  • With respect to the defect in interference and the level of crossing over, msh4 is similar to the zip1 mutant, which lacks a structural component of the synaptonemal complex (SC) [4].

Biological context of MSH4

  • MSH2, 3, and 6 function in mismatch repair in both vegetative and meiotic cells, whereas MSH4 and MSH5 act specifically to facilitate crossovers between homologs during meiosis [5].
  • EXO1 and MSH4 differentially affect crossing-over and segregation [6].
  • In the msh4 mutant, SC formation is delayed compared to wild type, and full synapsis is achieved in only about half of all nuclei [4].
  • Msh4 is not required for meiotic mismatch repair or gene conversion, but it is required for wild-type levels of crossing over [4].

Co-localisations of MSH4


Other interactions of MSH4


  1. Mutation of a meiosis-specific MutS homolog decreases crossing over but not mismatch correction. Ross-Macdonald, P., Roeder, G.S. Cell (1994) [Pubmed]
  2. The Arabidopsis MutS homolog AtMSH4 functions at an early step in recombination: evidence for two classes of recombination in Arabidopsis. Higgins, J.D., Armstrong, S.J., Franklin, F.C., Jones, G.H. Genes Dev. (2004) [Pubmed]
  3. 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]
  4. The budding yeast Msh4 protein functions in chromosome synapsis and the regulation of crossover distribution. Novak, J.E., Ross-Macdonald, P.B., Roeder, G.S. Genetics (2001) [Pubmed]
  5. Conserved properties between functionally distinct MutS homologs in yeast. Pochart, P., Woltering, D., Hollingsworth, N.M. J. Biol. Chem. (1997) [Pubmed]
  6. EXO1 and MSH4 differentially affect crossing-over and segregation. Khazanehdari, K.A., Borts, R.H. Chromosoma (2000) [Pubmed]
  7. Association between MSH4 (MutS homologue 4) and the DNA strand-exchange RAD51 and DMC1 proteins during mammalian meiosis. Neyton, S., Lespinasse, F., Moens, P.B., Paul, R., Gaudray, P., Paquis-Flucklinger, V., Santucci-Darmanin, S. Mol. Hum. Reprod. (2004) [Pubmed]
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