title: Phosphodependent recruitment of Bub1 and Bub3 to Spc7/KNL1 by Mph1 kinase maintains the spindle checkpoint.
abstract: The spindle assembly checkpoint (SAC) is the major surveillance system that ensures that sister chromatids do not separate until all chromosomes are correctly bioriented during mitosis. Components of the checkpoint include Mad1, Mad2, Mad3 (BubR1), Bub3, and the kinases Bub1, Mph1 (Mps1), and Aurora B. Checkpoint proteins are recruited to kinetochores when individual kinetochores are not bound to spindle microtubules or not under tension. Kinetochore association of Mad2 causes it to undergo a conformational change, which promotes its association to Mad3 and Cdc20 to form the mitotic checkpoint complex (MCC). The MCC inhibits the anaphase-promoting complex/cyclosome (APC/C) until the checkpoint is satisfied. SAC silencing derepresses Cdc20-APC/C activity. This triggers the polyubiquitination of securin and cyclin, which promotes the dissolution of sister chromatid cohesion and mitotic progression. We, and others, recently showed that association of PP1 to the Spc7/Spc105/KNL1 family of kinetochore proteins is necessary to stabilize microtubule-kinetochore attachments and silence the SAC. We now report that phosphorylation of the conserved MELT motifs in Spc7 by Mph1 (Mps1) recruits Bub1 and Bub3 to the kinetochore and that this is required to maintain the SAC signal.
authors.affiliation: Division of Biomedical Cell Biology, Warwick Medical School, University of Warwick, Gibbet Hill, Coventry, UK.
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Shepperd
authors.forename: John C
authors.initials: JC
authors.lastname: Meadows
authors.forename: Alicja M
authors.initials: AM
authors.lastname: Sochaj
authors.forename: Theresa C
authors.initials: TC
authors.lastname: Lancaster
authors.forename: Juan
authors.initials: J
authors.lastname: Zou
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Buttrick
authors.forename: Juri
authors.initials: J
authors.lastname: Rappsilber
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Hardwick
authors.forename: Jonathan B A
authors.initials: JB
authors.lastname: Millar
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D018386:Kinetochores / Q000378:metabolism*; D059566:M Phase Cell Cycle Checkpoints / Q000502:physiology*; D010766:Phosphorylation / Q000502:physiology; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C544653:Bub3 protein, S pombe; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D029702:Schizosaccharomyces pombe Proteins; C500242:Spc7 protein, S pombe; C570446:Mph1 protein, S pombe; D011494:Protein Kinases; C495594:Bub1 protein, S pombe; D017346:Protein Serine-Threonine Kinases