Pds1/Esp1-dependent and -independent sister chromatid separation in mutants defective for protein phosphatase 2A.
Spindle disruption or DNA damage prevents sister chromatid separation through the activation of checkpoint pathways that inhibit anaphase entry by stabilizing the anaphase inhibitor Pds1. Mutation of CDC55, which encodes a B regulatory subunit of protein phosphatase 2A (PP2A), results in precocious sister chromatid separation when spindle is disrupted. Here we report that decreased Pds1 levels in Deltacdc55 mutants contribute to sister chromatid separation in the presence of nocodazole, a microtubule-depolymerizing drug. However, in the presence of DNA damage, Deltacdc55 mutant cells separate sister chromatids without noticeable decrease of Pds1 or cohesin Mcd1/Scc1 levels. Further analysis demonstrates that Deltacdc55 mutants lose cohesion along the entire chromosomes when the spindle is disrupted. In contrast, separation of sister chromatids is limited to the centromeric regions in Deltacdc55 cells after DNA damage. Moreover, mutation of TPD3, which encodes the A regulatory subunit of PP2A, also results in sister chromatid separation in DNA- or spindle-damage-arrested cells. These data suggest that PP2A regulates sister chromatid cohesion in Pds1-dependent and -independent manners.
Tang
Xianying
X
Department of Biomedical Sciences, College of Medicine, Florida State University, 1115 West Call Street, Tallahassee, FL 32306, USA.
Wang
Yanchang
Y
D000705:Anaphase / Q000235:genetics; D064173:Anaphase-Promoting Complex-Cyclosome; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002503:Centromere / Q000235:genetics; D002842:Chromatids / Q000235:genetics*; D020090:Chromosome Segregation / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics; D004271:DNA, Fungal / Q000235:genetics; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D009154:Mutation / Q000235:genetics; D015739:Nocodazole / Q000494:pharmacology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D054648:Protein Phosphatase 2; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D064249:Securin; D064247:Separase; D008941:Spindle Apparatus / Q000235:genetics; D016615:Telomere / Q000235:genetics; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism
C071246:CDC55 protein, S cerevisiae; D018797:Cell Cycle Proteins; D004271:DNA, Fungal; D009687:Nuclear Proteins; C578004:PDS1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D064249:Securin; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D010450:Endopeptidases; C577986:ESP1 protein, S cerevisiae; D064247:Separase; D015739:Nocodazole