MSH5

MutS protein homolog 5 is a is_associated_with::protein that in humans is encoded by the MSH5 is_associated_with::gene.

MSH5 mutation in mouse and human
Mice homozygous for a null Msh5 mutation (Msh5-/-) are viable but sterile. In these mice, the prophase I stage of is_associated_with::meiosis is defective due to the disruption of chromosome pairing. This meiotic failure leads, in male mice, to diminution of testicular size, and in female mice, to a complete loss of ovarian structures.

A genetic investigation was performed to test women with premature ovarian failure for mutations in each of four meiotic genes. Among 41 women with premature ovarian failure two were found to be heterozygous for a mutation in the MSH5 gene; among 34 fertile women (controls) no mutations were found in the four tested genes.

These findings in mouse and human indicate that the MSH5 protein plays an important role in meiotic recombination.

MSH5 in Caenorhabditis elegans
In the worm Caenorhabditis elegans, the MSH5 protein is required during meiosis both for normal spontaneous and for gamma-irradiation induced crossover recombination and chiasma formation. Meiotic recombination is often initiated by double strand breaks. MSH5 mutants retain the competence to repair DNA double-strand breaks that are present during meiosis, but they accomplish this repair in a way that does not lead to crossovers between homologous chromosomes. The known mechanism of non-crossover recombinational repair is called synthesis dependent strand annealing (see is_associated_with::homologous recombination; see also Bernstein et al. ). MSH5 thus appears to be employed in directing the recombinational repair of some double-strand breaks towards the cross over option rather than the non-cross over option. Crossovers appear to be required for the fidelity of meiotic chromosome segregation and thus for progeny viability.

Interactions
MSH5 has been shown to interact with is_associated_with::MSH4.