Abstract
Faithful meiotic chromosome segregation and fertility require meiotic recombination between homologous chromosomes rather than the equally available sister chromatid, a bias that in Saccharomyces cerevisiae depends on the meiotic kinase, Mek1. Mek1 is thought to mediate repair template bias by specifically suppressing sister-directed repair. Instead, we found that when Mek1 persists on closely paired (synapsed) homologues, DNA repair is severely delayed, suggesting that Mek1 suppresses any proximal repair template. Accordingly, Mek1 is excluded from synapsed homologues in wild-type cells. Exclusion requires the AAA+-ATPase Pch2 and is directly coupled to synaptonemal complex assembly. Stage-specific depletion experiments further demonstrate that DNA repair in the context of synapsed homologues requires Rad54, a repair factor inhibited by Mek1. These data indicate that the sister template is distinguished from the homologue primarily by its closer proximity to inhibitory Mek1 activity. We propose that once pairing or synapsis juxtaposes homologues, exclusion of Mek1 is necessary to avoid suppression of all templates and accelerate repair progression.
Highlights
Meiosis is a specialized cell division that produces haploid gametes from diploid progenitors and is essential for sexual reproduction
To avoid meiotic chromosome segregation errors, recombination-mediated linkages are established between previously unattached homologous chromosomes
Meiotic repair-template bias in the budding yeast depends on the function of Mek1, a meiosis-specific protein
Summary
Meiosis is a specialized cell division that produces haploid gametes from diploid progenitors and is essential for sexual reproduction. The reduction in ploidy is achieved by a unique chromosome division phase (meiosis I) that segregates homologous chromosomes (homologues). Errors in this process are a leading cause of infertility, miscarriages, and birth defects in humans [1]. Proper meiosis I chromosome segregation in most organisms requires that each homologue pair be linked by at least one crossover. Crossover formation occurs during the extended prophase preceding meiosis I and is promoted by the programmed induction of DNA doublestrand breaks (DSBs). Resection of these breaks exposes single-stranded DNA tails that invade a donor template for repair. A subset of strand-invasion reactions subsequently matures to form double Holliday junctions, which are generally resolved as crossovers [2]
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