Cdk1 promotes kinetochore bi-orientation and regulates Cdc20 expression during recovery from spindle checkpoint arrest

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 r...

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Veröffentlicht in:The EMBO journal 2012-01, Vol.31 (2), p.403-416
Hauptverfasser: Liang, Hongqing, Lim, Hong Hwa, Venkitaraman, Ashok, Surana, Uttam
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creator Liang, Hongqing
Lim, Hong Hwa
Venkitaraman, Ashok
Surana, Uttam
description 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. A well‐characterized cell‐cycle checkpoint prevents mitotic chromosome segregation until all kinetochores are correctly attached to spindle microtubules. Here, the kinase CDK1 is implicated in the recovery from checkpoint arrest by regulating kinetochore bi‐orientation and APC/C activity.
doi_str_mv 10.1038/emboj.2011.385
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subjects Anaphase - physiology
Anaphase-Promoting Complex-Cyclosome
CDC2 Protein Kinase - antagonists & inhibitors
CDC2 Protein Kinase - physiology
Cdc20 Proteins
cell cycle
Cell Cycle Proteins - biosynthesis
Cell Cycle Proteins - genetics
Cell division
checkpoint
EMBO06
Gene expression
Gene Expression Regulation, Fungal
Kinetochores - physiology
Kinetochores - ultrastructure
M Phase Cell Cycle Checkpoints - physiology
Microtubules - physiology
Microtubules - ultrastructure
mitosis
Molecular biology
Nocodazole - pharmacology
Pharmacology
Pyrazoles - pharmacology
Pyrimidines - pharmacology
recovery
Saccharomyces cerevisiae - cytology
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Saccharomyces cerevisiae Proteins - biosynthesis
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - physiology
Spindle Apparatus - drug effects
Spindle Apparatus - physiology
Spindle Apparatus - ultrastructure
Ubiquitin-Protein Ligase Complexes - physiology
Yeast
Yeasts
title Cdk1 promotes kinetochore bi-orientation and regulates Cdc20 expression during recovery from spindle checkpoint arrest
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