title: Premature Silencing of the Spindle Assembly Checkpoint Is Prevented by the Bub1-H2A-Sgo1-PP2A Axis inSaccharomyces cerevisiae.
abstract: The spindle assembly checkpoint (SAC) monitors mistakes in kinetochore-microtubule interaction and its activation prevents anaphase entry. The SAC remains active until all chromosomes have achieved bipolar attachment which applies tension on kinetochores. Our previous data in budding yeastSaccharomyces cerevisiaeshow that Ipl1/Aurora B kinase and a centromere-associated protein, Sgo1, are required to prevent SAC silencing prior to tension generation, but we believe that this regulatory network is incomplete. Bub1 kinase is one of the SAC components, and Bub1-dependent H2A phosphorylation triggers centromere recruitment of Sgo1 by H2A in yeast and human cells. Although yeast cells lacking the kinase domain of Bub1 show competent SAC activation, we found that the mutant cells fail to maintain a prolonged checkpoint arrest in the presence of tensionless attachment. Mutation of the Bub1 phosphorylation site in H2A also results in premature SAC silencing in yeast cells. Previous data indicate that Sgo1 protein binds to PP2ARts1, and we found thatrts1Δ mutants exhibited premature SAC silencing as well. We further revealed thatsgo1mutants with abolished binding to H2A or PP2ARts1displayed premature SAC silencing. Together, our results suggest that, in budding yeastS. cerevisiae, the Bub1-H2A-Sgo1-PP2ARts1axis prevents SAC silencing and helps prolonged checkpoint arrest prior to tension establishment at kinetochores.
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, Florida 32306-4300.
authors.forename: Fengzhi
authors.initials: F
authors.lastname: Jin
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, Florida 32306-4300.
authors.forename: Michael
authors.initials: M
authors.lastname: Bokros
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, Florida 32306-4300 yanchang.wang@med.fsu.edu.
authors.forename: Yanchang
authors.identifier: 0000-0001-6782-0570
authors.initials: Y
authors.lastname: Wang
mesh_terms: D006657:Histones / Q000378:metabolism*; D059566:M Phase Cell Cycle Checkpoints; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C584280:Bub1 protein, S cerevisiae; D006657:Histones; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; C482640:Sgo1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D054648:Protein Phosphatase 2; C584366:Rts1 protein, S cerevisiae
keywords: Bub1 kinase; PP2A; SAC silencing; Sgo1; spindle assembly checkpoint