MutS protein homolog 5 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''MSH5''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Function
This gene encodes a member of the mutS family of proteins that are involved in DNA mismatch repair or meiotic recombination processes. This protein is similar to a Saccharomyces cerevisiae protein that participates in meiotic segregation fidelity and crossing-over. This protein forms heterooligomers with another member of this family, mutS homolog 4. Alternative splicing results in four transcript variants encoding three different isoforms.
Mutations
Mice
homozygous
Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism.
Mos ...
for a null Msh5 mutation (Msh5-/-) are viable but sterile.
In these mice, the
prophase I
Meiosis () is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, the sperm or egg cells. It involves two rounds of division that ultimately result in four cells, each with only one copy ...
stage of
meiosis
Meiosis () is a special type of cell division of germ cells in sexually-reproducing organisms that produces the gametes, the sperm or egg cells. It involves two rounds of division that ultimately result in four cells, each with only one c ...
is defective due to the disruption of
chromosome pairing. This meiotic failure leads, in male mice, to diminution of
testicular
A testicle or testis ( testes) is the gonad in all male bilaterians, including humans, and is homologous to the ovary in females. Its primary functions are the production of sperm and the secretion of androgens, primarily testosterone.
The r ...
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
Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism.
Mos ...
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.
In the worm ''
Caenorhabditis elegans
''Caenorhabditis elegans'' () is a free-living transparent nematode about 1 mm in length that lives in temperate soil environments. It is the type species of its genus. The name is a Hybrid word, blend of the Greek ''caeno-'' (recent), ''r ...
'', 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
homologous recombination
Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in Cell (biology), cellular organi ...
). MSH5 thus appears to be employed in directing the
recombinational repair
Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in Cell (biology), cellular organi ...
of some double-strand breaks towards the cross over option rather than the non-cross over option.
Interactions
MSH5 has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...
with
MSH4
MutS protein homolog 4 is a protein that in humans is encoded by the ''MSH4'' gene.
Function
The MSH4 and MSH5 proteins form a hetero-oligomeric structure (heterodimer) in yeast and humans. In the yeast ''Saccharomyces cerevisiae'' MSH4 and M ...
.
References
Further reading
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