A Mec1- and PP4-Dependent checkpoint couples centromere pairing to meiotic recombination

Jill E. Falk, Andrew Chi ho Chan, Eva Hoffmann, Andreas Hochwagen

Research output: Contribution to journalArticlepeer-review

Abstract

The faithful alignment of homologous chromosomes during meiotic prophase requires the coordination of DNA double-strand break (DSB) repair with large-scale chromosome reorganization. Here we identify the phosphatase PP4 (Pph3/Psy2) as a mediator of this process in Saccharomyces cerevisiae. In pp4 mutants, early stages of crossover repair and homology-independent pairing of centromeres are coordinately blocked. We traced the loss of centromere pairing to the persistent phosphorylation of the chromosomal protein Zip1 on serine 75. Zip1-S75 is a consensus site for the ATR-like checkpoint kinase Mec1, and centromere pairing is restored in mec1 mutants. Importantly, Zip1-S75 phosphorylation does not alter chromosome synapsis or DSB repair, indicating that Mec1 separates centromere pairing from the other functions of Zip1. The centromeric localization and persistent activity of PP4 during meiotic prophase suggest a model whereby Zip1-S75 phosphorylation dynamically destabilizes homology-independent centromere pairing in response to recombination initiation, thereby coupling meiotic chromosome dynamics to DSB repair.

Original languageEnglish (US)
Pages (from-to)599-611
Number of pages13
JournalDevelopmental Cell
Volume19
Issue number4
DOIs
StatePublished - Oct 19 2010

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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