Bub1 kinase targets Sgo1 to ensure efficient chromosome biorientation in budding yeast mitosis.
During cell division all chromosomes must be segregated accurately to each daughter cell. Errors in this process give rise to aneuploidy, which leads to birth defects and is implicated in cancer progression. The spindle checkpoint is a surveillance mechanism that ensures high fidelity of chromosome segregation by inhibiting anaphase until all kinetochores have established bipolar attachments to spindle microtubules. Bub1 kinase is a core component of the spindle checkpoint, and cells lacking Bub1 fail to arrest in response to microtubule drugs and precociously segregate their DNA. The mitotic role(s) of Bub1 kinase activity remain elusive, and it is controversial whether this C-terminal domain of Bub1p is required for spindle checkpoint arrest. Here we make a detailed analysis of budding yeast cells lacking the kinase domain (bub1DeltaK). We show that despite being able to arrest in response to microtubule depolymerisation and kinetochore-microtubule attachment defects, bub1DeltaK cells are sensitive to microtubule drugs. This is because bub1DeltaK cells display significant chromosome mis-segregation upon release from nocodazole arrest. bub1DeltaK cells mislocalise Sgo1p, and we demonstrate that both the Bub1 kinase domain and Sgo1p are required for accurate chromosome biorientation after nocodazole treatment. We propose that Bub1 kinase and Sgo1p act together to ensure efficient biorientation of sister chromatids during mitosis.
Fernius
Josefin
J
Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, United Kingdom.
Hardwick
Kevin G
KG
D045584:Chromosome Positioning / Q000187:drug effects; D020090:Chromosome Segregation / Q000187:drug effects; D015825:Chromosomes, Fungal / Q000378:metabolism; D018386:Kinetochores / Q000187:drug effects / Q000378:metabolism; D050296:Microbial Viability / Q000187:drug effects; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D009154:Mutation; D015739:Nocodazole / Q000494:pharmacology; D009687:Nuclear Proteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D004718:Saccharomycetales / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D008941:Spindle Apparatus / Q000187:drug effects / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology
D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; C482640:Sgo1 protein, S cerevisiae; D050257:Tubulin Modulators; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases; D015739:Nocodazole