Chromosome Synapsis Alleviates Mek1-Dependent Suppression of Meiotic DNA Repair

Vijayalakshmi V. Subramanian, Amy J. MacQueen, Gerben Vader, Miki Shinohara, Aurore Sanchez, Valérie Borde, Akira Shinohara, Andreas Hochwagen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Article numbere1002369
JournalPloS Biology
Volume14
Issue number2
DOIs
Publication statusPublished - 12 Feb 2016
Externally publishedYes

Cite this

Subramanian, V. V., MacQueen, A. J., Vader, G., Shinohara, M., Sanchez, A., Borde, V., ... Hochwagen, A. (2016). Chromosome Synapsis Alleviates Mek1-Dependent Suppression of Meiotic DNA Repair. PloS Biology, 14(2), [e1002369]. https://doi.org/10.1371/journal.pbio.1002369