MSH4

MutS protein homolog 4 is a is_associated_with::protein that in humans is encoded by the MSH4 is_associated_with::gene.

is_associated_with::Meiosis
The MSH4 and MSH5 proteins form a hetero-oligomeric structure (heterodimer) in yeast and humans. In the yeast is_associated_with::Saccharomyces cerevisiae MSH4 and MSH5 act specifically to facilitate crossovers between is_associated_with::homologous chromosomes during is_associated_with::meiosis and were also thought to ensure the proper segregation of chromosomes to opposite poles at the first meiotic division. The MSH4/MSH5 complex binds and stabilizes double is_associated_with::Holliday junctions and promotes their resolution into crossover products. An MSH4 hypomorphic (partially functional) mutant of S. cerevisiae showed a 30% genome wide reduction in crossover numbers, and a large number of meioses with non exchange chromosomes. Nevertheless this mutant gave rise to spore viability patterns suggesting that segregation of non-exchange chromosomes occurred efficiently. Thus, in S. cerevisiae, proper segregation apparently does not entirely depend on crossovers between homologous pairs.

The him-14 gene of the worm is_associated_with::Caenorhabditis elegans encodes an ortholog of MSH4. Formation of crossovers during C. elegans meiosis requires the him-14(MSH4) gene. Loss of him-14(MSH-4) function severely reduces crossing over, resulting in lack of chiasmata between homologs and consequent missegregation. Thus, in C. elegans, segregation apparently does depend on crossovers between homologous pairs. Him-14(MSH4) functions during the pachytene stage of meiosis, indicating that it is not needed for establishing the preceding stages of pairing and synapsis of homologous chromosomes.

In an MSH4 mutant of rice, chiasma frequency was dramatically decreased to about 10% of the wild-type frequency, although the synaptonemal complex was normally installed. is_associated_with::MSH5 thus acts alone to promote the majority of crossovers during rice meiosis.

In general it appears that MSH5 acts during meiosis to direct the recombinational repair of some DNA double-strand breaks towards the crossover option rather than the non-cross over option (see is_associated_with::Homologous recombination).

Interactions
MSH4 has been shown to interact with is_associated_with::MLH1, is_associated_with::MSH5  and is_associated_with::MLH3.