Mek1 kinase governs outcomes of meiotic recombination and the checkpoint response

Hsin Yen Wu, Hsuan Chung Ho, Sean M. Burgess

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Background: Homologous recombination promotes proper segregation of chromosomes during meiosis. Programmed double-strand breaks (DSBs) initiate recombination and are repaired preferentially using the homolog rather than the sister chromatid template. In yeast, activation of Mek1 kinase upholds this bias. Mek1 is also a proposed effector kinase in the recombination checkpoint that responds to aberrant DNA and/or axis structures. Elucidating a role for Mek1 in this checkpoint has been difficult, because a mek1 null mutation causes rapid repair of DSBs using a sister chromatid, thus bypassing formation of checkpoint-activating lesions. Here we analyzed a MEK1 gain-of-function allele to test if it would enhance interhomolog bias and/or the checkpoint response. Results: When Mek1 activation was artificially maintained through glutathione S-transferase-mediated dimerization, there was an enhanced skew toward interhomolog recombination and reduction of intersister events, including multichromatid joint molecules. Increased interhomolog events were specifically repaired as noncrossovers rather than as crossovers. Ectopic Mek1 dimerization was also sufficient to impose interhomolog bias in the absence of recombination checkpoint functions, thereby uncoupling these two processes. Finally, the stringency of the checkpoint response was enhanced in mutants with weak recombination defects by blocking prophase exit in a subset of cells in which arrest is not absolute. Conclusions: We propose that Mek1 plays dual roles during meiotic prophase I by phosphorylating targets directly involved in the recombination checkpoint, as well as targets involved in sister chromatid recombination. We discuss how regulation of pachytene exit by Mek1 or similar kinases could influence checkpoint stringency, which may differ among species and between sexes.

Original languageEnglish (US)
Pages (from-to)1707-1716
Number of pages10
JournalCurrent Biology
Volume20
Issue number19
DOIs
StatePublished - Oct 12 2010

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ASJC Scopus subject areas

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

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