title: Cdk1 promotes kinetochore bi-orientation and regulates Cdc20 expression during recovery from spindle checkpoint arrest.
abstract: The spindle assembly checkpoint (SAC), an evolutionarily conserved surveillance pathway, prevents chromosome segregation in response to conditions that disrupt the kinetochore-microtubule attachment. Removal of the checkpoint-activating stimulus initiates recovery during which spindle integrity is restored, kinetochores become bi-oriented, and cells initiate anaphase. Whether recovery ensues passively after the removal of checkpoint stimulus, or requires mediation by specific effectors remains uncertain. Here, we report two unrecognized functions of yeast Cdk1 required for efficient recovery from SAC-induced arrest. We show that Cdk1 promotes kinetochore bi-orientation during recovery by restraining premature spindle elongation thereby extinguishing SAC signalling. Moreover, Cdk1 is essential for sustaining the expression of Cdc20, an activator of the anaphase promoting complex/cyclosome (APC/C) required for anaphase progression. We suggest a model in which Cdk1 activity promotes recovery from SAC-induced mitotic arrest by regulating bi-orientation and APC/C activity. Our findings provide fresh insights into the regulation of mitosis and have implications for the therapeutic efficacy of anti-mitotic drugs.
authors: Institute of Molecular and Cell Biology, A STAR (Agency for Science Technology and Research), Singapore.
authors: Hongqing
authors: H
authors: Liang
authors: Hong Hwa
authors: HH
authors: Lim
authors: Ashok
authors: A
authors: Venkitaraman
authors: Uttam
authors: U
authors: Surana
mesh_terms: D000705:Anaphase / Q000502:physiology; D064173:Anaphase-Promoting Complex-Cyclosome; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors / Q000502:physiology*; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D018386:Kinetochores / Q000502:physiology* / Q000648:ultrastructure; D059566:M Phase Cell Cycle Checkpoints / Q000502:physiology*; D008870:Microtubules / Q000502:physiology / Q000648:ultrastructure; D015739:Nocodazole / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008941:Spindle Apparatus / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D043743:Ubiquitin-Protein Ligase Complexes / Q000502:physiology*
chemical_list: C479693:1-tert-butyl-3-naphthalen-1-ylmethyl-1H-pyrazolo(3,4-d)pyrimidin-4-ylemine; C577495:CDC20 protein, S cerevisiae; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; D011720:Pyrazoles; D011743:Pyrimidines; D029701:Saccharomyces cerevisiae Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D016203:CDC2 Protein Kinase; D015739:Nocodazole