Competing crossover pathways act during meiosis in Saccharomyces cerevisiae

Area of Science:

• Genetics
• Molecular Biology
• Yeast Research

Background:

• Meiotic recombination is crucial for accurate chromosome segregation.
• Several protein complexes, including MSH4-MSH5, MLH1-MLH3, and MUS81-MMS4, are known to influence crossing over in Saccharomyces cerevisiae.
• The precise roles and interplay of these complexes in regulating crossover pathways and interference remain incompletely understood.

Purpose of the Study:

• To elucidate the distinct roles of MSH4-MSH5, MLH1-MLH3, and MUS81-MMS4 complexes in meiotic crossing over.
• To analyze the genetic interactions between mutations in these complexes.
• To identify and characterize different crossover pathways in yeast.

Main Methods:

• Analysis of meiotic crossing over frequencies in single, double, and triple mutants of msh5Δ, mlh1Δ, and mms4Δ in Saccharomyces cerevisiae.
• Utilized newly developed computer software for analyzing crossover events across four consecutive genetic intervals on chromosome XV.
• Assessed spore viability in mutant strains to evaluate the impact on meiotic fidelity.

Main Results:

• mlh1Δ mms4Δ double mutants exhibited the most significant reduction in crossing over (13- to 15-fold) with relatively high spore viability (42%).
• msh5Δ mms4Δ and msh5Δ mms4Δ mlh1Δ mutants showed less severe reductions in crossing over (4- to 6-fold) but had lower spore viability (18-19%).
• These findings suggest distinct contributions of the analyzed complexes to different crossover pathways.

Conclusions:

• Meiotic crossing over in yeast operates through at least three distinct pathways.
• MUS81-MMS4 promotes interference-independent crossing over.
• MSH4-MSH5 and MLH1-MLH3 collaborate to promote interference-dependent crossovers, and MSH4-MSH5 may repress a pathway generating deleterious crossovers.