Genetic analysis of baker's yeast msh4-msh5 reveals a threshold crossover level for meiotic viability

During meiosis,the msh4-msh5 complex is thought to stabilize single-end invasion intermediates that form during early stages of recombination and subsequently bind to holliday junctions to facilitate crossover formation. to analyze msh4-msh5 function,we mutagenized 57 residues in saccharomyces cerevisiae msh4 and msh5 that are either conserved across all msh4/5 family members or are specific to msh4 and msh5. the msh5 subunit appeared more sensitive to mutagenesis. we identified msh4 and msh5 threshold (msh4/5-t) mutants that showed wild-type spore viability and crossover interference but displayed,compared to wild-type,up to a two-fold decrease in crossing over on large and medium sized chromosomes (xv,vii,viii). crossing over on a small chromosome,however,approached wild-type levels. the msh4/5-t mutants also displayed synaptonemal complex assembly defects. a triple mutant containing a msh4/5-t allele and mutations that decreased meiotic double-strand break levels (spo11-ha) and crossover interference (pch2δ) showed synergistic defects in spore viability. together these results indicate that the baker's yeast meiotic cell does not require the ~90 crossovers maintained by crossover homeostasis to form viable spores. they also show that pch2-mediated crossover interference is important to maintain meiotic viability when crossovers become limiting. © 2010 nishant et al.