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

Research output: Contribution to journalArticle

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 (US)
Article numbere1002369
JournalPLoS Biology
Volume14
Issue number2
DOIs
StatePublished - Feb 12 2016

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Chromosome Pairing
chromosome pairing
Chromosomes
DNA repair
DNA Repair
Repair
Synaptonemal Complex
synaptonemal complex
Chromosome Segregation
Chromatids
chromosome segregation
chromatids
DNA
Genetic Recombination
adenosinetriphosphatase
Fertility
Saccharomyces cerevisiae
Adenosine Triphosphatases
phosphotransferases (kinases)
Phosphotransferases

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

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

Chromosome Synapsis Alleviates Mek1-Dependent Suppression of Meiotic DNA Repair. / Subramanian, Vijayalakshmi V.; MacQueen, Amy J.; Vader, Gerben; Shinohara, Miki; Sanchez, Aurore; Borde, Valérie; Shinohara, Akira; Hochwagen, Andreas.

In: PLoS Biology, Vol. 14, No. 2, e1002369, 12.02.2016.

Research output: Contribution to journalArticle

Subramanian, VV, MacQueen, AJ, Vader, G, Shinohara, M, Sanchez, A, Borde, V, Shinohara, A & Hochwagen, A 2016, 'Chromosome Synapsis Alleviates Mek1-Dependent Suppression of Meiotic DNA Repair', PLoS Biology, vol. 14, no. 2, e1002369. https://doi.org/10.1371/journal.pbio.1002369
Subramanian VV, MacQueen AJ, Vader G, Shinohara M, Sanchez A, Borde V et al. Chromosome Synapsis Alleviates Mek1-Dependent Suppression of Meiotic DNA Repair. PLoS Biology. 2016 Feb 12;14(2). e1002369. https://doi.org/10.1371/journal.pbio.1002369
Subramanian, Vijayalakshmi V. ; MacQueen, Amy J. ; Vader, Gerben ; Shinohara, Miki ; Sanchez, Aurore ; Borde, Valérie ; Shinohara, Akira ; Hochwagen, Andreas. / Chromosome Synapsis Alleviates Mek1-Dependent Suppression of Meiotic DNA Repair. In: PLoS Biology. 2016 ; Vol. 14, No. 2.
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