Mus81 and Yen1 Promote Reciprocal Exchange during Mitotic Recombination to Maintain Genome Integrity in Budding Yeast

SummaryHolliday junction (HJ) resolution is required for segregation of chromosomes and for formation of crossovers during homologous recombination. The identity of the resolvase(s) that functions in vivo has yet to be established, although several proteins able to cut HJs in vitro have been identified as candidates in yeasts and mammals. Using an assay to detect unselected products of mitotic recombination, we found a significant decrease in crossovers in the Saccharomyces cerevisiae mus81Δ mutant. Yen1 serves a backup function responsible for resolving intermediates in mus81Δ mutants, or when conversion tracts are short. In the absence of both Mus81 and Yen1, intermediates are not channeled exclusively to noncrossover recombinants, but instead are processed by Pol32-dependent break-induced replication (BIR). The channeling of recombination from reciprocal exchange to BIR results in greatly increased spontaneous loss of heterozygosity (LOH) and chromosome mis-segregation in the mus81Δ yen1Δ mutant, typical of the genomic instability found in tumor cells.

Graphical AbstractFigure optionsDownload high-quality image (188 K)Download as PowerPoint slideHighlights
► Mus81-Mms4 cleaves mitotic strand invasion intermediates to form crossovers
► Yen1 provides a backup function in the absence of Mus81-Mms4
► Pol32 extends DNA synthesis tracts promoting crossovers
► LOH by chromosome loss and break-induced replication increases in mus81Δ yen1Δ mutants