title: The Pch2 AAA+ ATPase promotes phosphorylation of the Hop1 meiotic checkpoint adaptor in response to synaptonemal complex defects.
abstract: Meiotic cells possess surveillance mechanisms that monitor critical events such as recombination and chromosome synapsis. Meiotic defects resulting from the absence of the synaptonemal complex component Zip1 activate a meiosis-specific checkpoint network resulting in delayed or arrested meiotic progression. Pch2 is an evolutionarily conserved AAA+ ATPase required for the checkpoint-induced meiotic block in the zip1 mutant, where Pch2 is only detectable at the ribosomal DNA array (nucleolus). We describe here that high levels of the Hop1 protein, a checkpoint adaptor that localizes to chromosome axes, suppress the checkpoint defect of a zip1 pch2 mutant restoring Mek1 activity and meiotic cell cycle delay. We demonstrate that the critical role of Pch2 in this synapsis checkpoint is to sustain Mec1-dependent phosphorylation of Hop1 at threonine 318. We also show that the ATPase activity of Pch2 is essential for its checkpoint function and that ATP binding to Pch2 is required for its localization. Previous work has shown that Pch2 negatively regulates Hop1 chromosome abundance during unchallenged meiosis. Based on our results, we propose that, under checkpoint-inducing conditions, Pch2 also possesses a positive action on Hop1 promoting its phosphorylation and its proper distribution on unsynapsed chromosome axes.
authors.affiliation: Instituto de Biología Funcional y Genómica. Consejo Superior de Investigaciones Científicas and University of Salamanca, 37007 Salamanca, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Herruzo
authors.affiliation: Instituto de Biología Funcional y Genómica. Consejo Superior de Investigaciones Científicas and University of Salamanca, 37007 Salamanca, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Ontoso
authors.affiliation: Instituto de Biología Funcional y Genómica. Consejo Superior de Investigaciones Científicas and University of Salamanca, 37007 Salamanca, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: González-Arranz
authors.affiliation: Instituto de Biología Funcional y Genómica. Consejo Superior de Investigaciones Científicas and University of Salamanca, 37007 Salamanca, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Cavero
authors.affiliation: Instituto de Biología Funcional y Genómica. Consejo Superior de Investigaciones Científicas and University of Salamanca, 37007 Salamanca, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Lechuga
authors.affiliation: Instituto de Biología Funcional y Genómica. Consejo Superior de Investigaciones Científicas and University of Salamanca, 37007 Salamanca, Spain pedross@usal.es.
authors.forename: Pedro A
authors.initials: PA
authors.lastname: San-Segundo
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D001665:Binding Sites; D059447:Cell Cycle Checkpoints; D023902:Chromosome Pairing; D053903:DNA Breaks, Double-Stranded; D004268:DNA-Binding Proteins / Q000378:metabolism*; D016153:Genes, Suppressor; D005820:Genetic Testing; D008540:Meiosis; D050296:Microbial Viability; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D013172:Spores, Fungal / Q000502:physiology; D013573:Synaptonemal Complex / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C086672:HOP1 protein, S cerevisiae; D009687:Nuclear Proteins; C528119:Pch2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000255:Adenosine Triphosphate; D010749:Phosphoprotein Phosphatases; D000251:Adenosine Triphosphatases