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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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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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.</description><identifier>ISSN: 0261-4189</identifier><identifier>EISSN: 1460-2075</identifier><identifier>DOI: 10.1038/emboj.2011.385</identifier><identifier>PMID: 22056777</identifier><identifier>CODEN: EMJODG</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>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</subject><ispartof>The EMBO journal, 2012-01, Vol.31 (2), p.403-416</ispartof><rights>European Molecular Biology Organization 2012</rights><rights>Copyright © 2012 European Molecular Biology Organization</rights><rights>Copyright Nature Publishing Group Jan 18, 2012</rights><rights>Copyright © 2012, European Molecular Biology Organization 2012 European Molecular Biology Organization</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5705-7442e63c937fea195cfb46c10b18a3356896f065fd4ab4d883577acad4caa0b93</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3261552/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3261552/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,1411,1427,27901,27902,41096,42165,45550,45551,46384,46808,51551,53766,53768</link.rule.ids><linktorsrc>$$Uhttps://doi.org/10.1038/emboj.2011.385$$EView_record_in_Springer_Nature$$FView_record_in_$$GSpringer_Nature</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22056777$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liang, Hongqing</creatorcontrib><creatorcontrib>Lim, Hong Hwa</creatorcontrib><creatorcontrib>Venkitaraman, Ashok</creatorcontrib><creatorcontrib>Surana, Uttam</creatorcontrib><title>Cdk1 promotes kinetochore bi-orientation and regulates Cdc20 expression during recovery from spindle checkpoint arrest</title><title>The EMBO journal</title><addtitle>EMBO J</addtitle><addtitle>EMBO J</addtitle><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.</description><subject>Anaphase - physiology</subject><subject>Anaphase-Promoting Complex-Cyclosome</subject><subject>CDC2 Protein Kinase - antagonists & inhibitors</subject><subject>CDC2 Protein Kinase - physiology</subject><subject>Cdc20 Proteins</subject><subject>cell cycle</subject><subject>Cell Cycle Proteins - biosynthesis</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Cell division</subject><subject>checkpoint</subject><subject>EMBO06</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Fungal</subject><subject>Kinetochores - physiology</subject><subject>Kinetochores - ultrastructure</subject><subject>M Phase Cell Cycle Checkpoints - physiology</subject><subject>Microtubules - physiology</subject><subject>Microtubules - ultrastructure</subject><subject>mitosis</subject><subject>Molecular biology</subject><subject>Nocodazole - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The EMBO journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Liang, Hongqing</au><au>Lim, Hong Hwa</au><au>Venkitaraman, Ashok</au><au>Surana, Uttam</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cdk1 promotes kinetochore bi-orientation and regulates Cdc20 expression during recovery from spindle checkpoint arrest</atitle><jtitle>The EMBO journal</jtitle><stitle>EMBO J</stitle><addtitle>EMBO J</addtitle><date>2012-01-18</date><risdate>2012</risdate><volume>31</volume><issue>2</issue><spage>403</spage><epage>416</epage><pages>403-416</pages><issn>0261-4189</issn><eissn>1460-2075</eissn><coden>EMJODG</coden><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.
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.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>22056777</pmid><doi>10.1038/emboj.2011.385</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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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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