title: Requirement of Skp1-Bub1 interaction for kinetochore-mediated activation of the spindle checkpoint.
abstract: The spindle checkpoint transiently prevents cell cycle progression of cells that have incurred errors or failed to complete steps during mitosis, including those involving kinetochore function. The molecular nature of the primary signal transmitted from defective kinetochores and how it is detected by the spindle checkpoint are unknown. We report biochemical evidence that Bub1, a component of the spindle checkpoint, associates with centromere (CEN) DNA via Skp1, a core kinetochore component in budding yeast. The Skp1's interaction with Bub1 is required for the mitotic delay induced by kinetochore tension defects, but not for the arrest induced by spindle depolymerization, kinetochore assembly defects, or Mps1 overexpression. We propose that the Skp1-Bub1 interaction is important for transmitting a signal to the spindle checkpoint pathway when insufficient tension is present at kinetochores.
authors.affiliation: Department of Molecular Pharmacology, St. Jude Children's Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105, USA. katsumi.kitagawa@stjude.org
authors.forename: Katsumi
authors.initials: K
authors.lastname: Kitagawa
authors.forename: Rashid
authors.initials: R
authors.lastname: Abdulle
authors.forename: Parmil K
authors.initials: PK
authors.lastname: Bansal
authors.forename: Gerard
authors.initials: G
authors.lastname: Cagney
authors.forename: Stanley
authors.initials: S
authors.lastname: Fields
authors.forename: Philip
authors.initials: P
authors.lastname: Hieter
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001542:Benomyl / Q000494:pharmacology; D002478:Cells, Cultured; D002503:Centromere / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D005057:Eukaryotic Cells / Q000378:metabolism*; D044783:F-Box Proteins; D018816:Genes, cdc / Q000502:physiology*; D018386:Kinetochores / Q000378:metabolism*; D008938:Mitosis / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D044843:SKP Cullin F-Box Protein Ligases; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction / Q000235:genetics; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism*; D013314:Stress, Mechanical
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D044783:F-Box Proteins; D029701:Saccharomyces cerevisiae Proteins; D004247:DNA; D044843:SKP Cullin F-Box Protein Ligases; C120507:SKP1 protein, S cerevisiae; D011494:Protein Kinases; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases; D001542:Benomyl