title: Spindle checkpoint silencing requires association of PP1 to both Spc7 and kinesin-8 motors.
abstract: The spindle checkpoint is the prime cell-cycle control mechanism that ensures sister chromatids are bioriented before anaphase takes place. Aurora B kinase, the catalytic subunit of the chromosome passenger complex, both destabilizes kinetochore attachments that do not generate tension and simultaneously maintains the spindle checkpoint signal. However, it is unclear how the checkpoint is silenced following chromosome biorientation. We demonstrate that association of type 1 phosphatase (PP1(Dis2)) with both the N terminus of Spc7 and the nonmotor domains of the Klp5-Klp6 (kinesin-8) complex is necessary to counteract Aurora B kinase to efficiently silence the spindle checkpoint. The role of Klp5 and Klp6 in checkpoint silencing is specific to this class of kinesin and independent of their motor activities. These data demonstrate that at least two distinct pools of PP1, one kinetochore associated and the other motor associated, are needed to silence the spindle checkpoint.
authors.affiliation: Division of Biomedical Cell Biology, Warwick Medical School, University of Warwick, Gibbet Hill, Coventry, UK.
authors.forename: John C
authors.initials: JC
authors.lastname: Meadows
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Shepperd
authors.forename: Vincent
authors.initials: V
authors.lastname: Vanoosthuyse
authors.forename: Theresa C
authors.initials: TC
authors.lastname: Lancaster
authors.forename: Alicja M
authors.initials: AM
authors.lastname: Sochaj
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Buttrick
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Hardwick
authors.forename: Jonathan B A
authors.initials: JB
authors.lastname: Millar
mesh_terms: D000595:Amino Acid Sequence; D002842:Chromatids; D047369:Chromatin Immunoprecipitation; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D018386:Kinetochores / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D008941:Spindle Apparatus / Q000502:physiology*; D020798:Two-Hybrid System Techniques
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D008869:Microtubule-Associated Proteins; D029702:Schizosaccharomyces pombe Proteins; C500242:Spc7 protein, S pombe; C502092:Dis2 protein, S pombe; D010749:Phosphoprotein Phosphatases; C404792:SDS21 protein, S pombe; C469734:Klp5 protein, S pombe; C459102:Klp6 protein, S pombe; D016547:Kinesins