Pch2 acts through Xrs2 and Tel1/ATM to modulate interhomolog bias and checkpoint function during meiosis

PLoS Genet. 2011 Nov;7(11):e1002351. doi: 10.1371/journal.pgen.1002351. Epub 2011 Nov 3.

Abstract

Proper segregation of chromosomes during meiosis requires the formation and repair of double-strand breaks (DSBs) to form crossovers. Repair is biased toward using the homolog as a substrate rather than the sister chromatid. Pch2 is a conserved member of the AAA(+)-ATPase family of proteins and is implicated in a wide range of meiosis-specific processes including the recombination checkpoint, maturation of the chromosome axis, crossover control, and synapsis. We demonstrate a role for Pch2 in promoting and regulating interhomolog bias and the meiotic recombination checkpoint in response to unprocessed DSBs through the activation of axial proteins Hop1 and Mek1 in budding yeast. We show that Pch2 physically interacts with the putative BRCT repeats in the N-terminal region of Xrs2, a member of the MRX complex that acts at sites of unprocessed DSBs. Pch2, Xrs2, and the ATM ortholog Tel1 function in the same pathway leading to the phosphorylation of Hop1, independent of Rad17 and the ATR ortholog Mec1, which respond to the presence of single-stranded DNA. An N-terminal deletion of Xrs2 recapitulates the pch2Δ phenotypes for signaling unresected breaks. We propose that interaction with Xrs2 may enable Pch2 to remodel chromosome structure adjacent to the site of a DSB and thereby promote accessibility of Hop1 to the Tel1 kinase. In addition, Xrs2, like Pch2, is required for checkpoint-mediated delay conferred by the failure to synapse chromosomes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism
  • Cell Cycle Proteins / genetics
  • Chromosome Pairing
  • Chromosome Segregation / genetics
  • Chromosomes, Fungal / genetics*
  • Crossing Over, Genetic / genetics
  • DNA Breaks, Double-Stranded
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • G2 Phase Cell Cycle Checkpoints
  • Intracellular Signaling Peptides and Proteins / genetics*
  • MAP Kinase Kinase 1 / genetics
  • Meiosis / genetics*
  • Nuclear Proteins / genetics*
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / genetics*
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins / genetics*
  • Terminal Repeat Sequences

Substances

  • ATM1 protein, S cerevisiae
  • ATP-Binding Cassette Transporters
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • HOP1 protein, S cerevisiae
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • Pch2 protein, S cerevisiae
  • RAD17 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • XRS2 protein, S cerevisiae
  • Protein-Serine-Threonine Kinases
  • TEL1 protein, S cerevisiae
  • MAP Kinase Kinase 1
  • Adenosine Triphosphatases