A Mec1- and PP4-dependent checkpoint couples centromere pairing to meiotic recombination.
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.
Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Jill E
JE
Falk
Andrew Chi-ho
AC
Chan
Eva
E
Hoffmann
Andreas
A
Hochwagen
D002503:Centromere / Q000378:metabolism*; D023902:Chromosome Pairing; D003434:Crossing Over, Genetic; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction; D013379:Substrate Specificity; D013573:Synaptonemal Complex / Q000378:metabolism; D013696:Temperature
D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C494616:Psy2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C090118:Zip1 protein, S cerevisiae; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C502440:PPH3 protein, S cerevisiae; D010749:Phosphoprotein Phosphatases