Editing Chromosomal crossover (section)

===MSH4 and MSH5===
The MSH4 and MSH5 proteins form a hetero-oligomeric structure ([[Protein dimer|heterodimer]]) in yeast and humans.<ref name=Pochart>{{cite journal | vauthors = Pochart P, Woltering D, Hollingsworth NM | title = Conserved properties between functionally distinct MutS homologs in yeast | journal = The Journal of Biological Chemistry | volume = 272 | issue = 48 | pages = 30345–30349 | date = November 1997 | pmid = 9374523 | doi = 10.1074/jbc.272.48.30345 | doi-access = free }}</ref><ref name="pmid9787078">{{cite journal | vauthors = Winand NJ, Panzer JA, Kolodner RD | title = Cloning and characterization of the human and Caenorhabditis elegans homologs of the Saccharomyces cerevisiae MSH5 gene | journal = Genomics | volume = 53 | issue = 1 | pages = 69–80 | date = October 1998 | pmid = 9787078 | doi = 10.1006/geno.1998.5447 | doi-access = free }}</ref><ref name="pmid10029069">{{cite journal | vauthors = Bocker T, Barusevicius A, Snowden T, Rasio D, Guerrette S, Robbins D, Schmidt C, Burczak J, Croce CM, Copeland T, Kovatich AJ, Fishel R | display-authors = 6 | title = hMSH5: a human MutS homologue that forms a novel heterodimer with hMSH4 and is expressed during spermatogenesis | journal = Cancer Research | volume = 59 | issue = 4 | pages = 816–822 | date = February 1999 | pmid = 10029069 }}</ref>  In the yeast ''[[Saccharomyces cerevisiae]]'', MSH4 and MSH5 act specifically to facilitate crossovers between [[homologous chromosome]]s during [[meiosis]].<ref name=Pochart />  The MSH4/MSH5 complex binds and stabilizes double [[Holliday junction]]s and promotes their resolution into crossover products.  An MSH4 [[Muller's morphs#Hypomorph|hypomorphic]] (partially functional) mutant of ''S. cerevisiae'' showed a 30% genome-wide reduction in crossover numbers and a large number of [[Meiosis|meioses]] with non-exchange chromosomes.<ref name="pmid25467183">{{cite journal | vauthors = Krishnaprasad GN, Anand MT, Lin G, Tekkedil MM, Steinmetz LM, Nishant KT | title = Variation in crossover frequencies perturb crossover assurance without affecting meiotic chromosome segregation in Saccharomyces cerevisiae | journal = Genetics | volume = 199 | issue = 2 | pages = 399–412 | date = February 2015 | pmid = 25467183 | pmc = 4317650 | doi = 10.1534/genetics.114.172320 }}</ref>  Nevertheless, this [[mutant]] gave rise to [[spore]] viability patterns suggesting that [[Chromosome segregation|segregation]] of non-exchange chromosomes occurred efficiently.  Thus in ''S. cerevisiae'' proper segregation apparently does not entirely depend on crossovers between [[Homologous chromosome|homologous]] pairs.{{cn|date=December 2024}} In humans, biallelic loss of function variants to MSH4 and MSH5 are compatible with life, but are associated with azospermia in males (spermatogenic failure) and premature ovarian failure in females.<ref>{{cite web |url=https://www.omim.org/entry/602105 |title=Entry - *602105 - MutS HOMOLOG 4; MSH4 - OMIM }}</ref><ref>{{cite web |url=https://www.omim.org/entry/603382?search=msh5&highlight=msh5 | title=Entry - *603382 - MutS HOMOLOG 5; MSH5 - OMIM }}</ref>
[[File:Meiosis crossover.png|thumb|Chiasma is the point of crossing over of the arms of sister chromatids.  ]]