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CDK-dependent phosphorylation and nuclear exclusion coordinately control kinetochore assembly state
Accurate chromosome segregation requires assembly of the multiprotein kinetochore complex. Prior work has identified more than 100 different kinetochore components in human cells. However, little is known about the regulatory processes that specify their assembly upon mitotic entry and disassembly a...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3613690/ https://www.ncbi.nlm.nih.gov/pubmed/23530067 http://dx.doi.org/10.1083/jcb.201301006 |
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author | Gascoigne, Karen E. Cheeseman, Iain M. |
author_facet | Gascoigne, Karen E. Cheeseman, Iain M. |
author_sort | Gascoigne, Karen E. |
collection | PubMed |
description | Accurate chromosome segregation requires assembly of the multiprotein kinetochore complex. Prior work has identified more than 100 different kinetochore components in human cells. However, little is known about the regulatory processes that specify their assembly upon mitotic entry and disassembly at mitotic exit. In this paper, we used a live-cell imaging–based assay to quantify kinetochore disassembly kinetics and systematically analyze the role of potential regulatory mechanisms in controlling kinetochore assembly state. We find that kinetochore assembly and disassembly was driven primarily by mitotic phosphorylation downstream of cyclin-dependent kinase (CDK). In addition, we demonstrate that nuclear exclusion of the Ndc80 complex helped restrict kinetochore formation to mitosis. Combining constitutive CDK-dependent phosphorylation of CENP-T and forced nuclear localization of the Ndc80 complex partially prevented kinetochore disassembly at mitotic exit and led to chromosome segregation defects in subsequent divisions. In total, we find that the coordinated temporal regulation of outer kinetochore assembly is essential for accurate cell division. |
format | Online Article Text |
id | pubmed-3613690 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-36136902013-10-01 CDK-dependent phosphorylation and nuclear exclusion coordinately control kinetochore assembly state Gascoigne, Karen E. Cheeseman, Iain M. J Cell Biol Research Articles Accurate chromosome segregation requires assembly of the multiprotein kinetochore complex. Prior work has identified more than 100 different kinetochore components in human cells. However, little is known about the regulatory processes that specify their assembly upon mitotic entry and disassembly at mitotic exit. In this paper, we used a live-cell imaging–based assay to quantify kinetochore disassembly kinetics and systematically analyze the role of potential regulatory mechanisms in controlling kinetochore assembly state. We find that kinetochore assembly and disassembly was driven primarily by mitotic phosphorylation downstream of cyclin-dependent kinase (CDK). In addition, we demonstrate that nuclear exclusion of the Ndc80 complex helped restrict kinetochore formation to mitosis. Combining constitutive CDK-dependent phosphorylation of CENP-T and forced nuclear localization of the Ndc80 complex partially prevented kinetochore disassembly at mitotic exit and led to chromosome segregation defects in subsequent divisions. In total, we find that the coordinated temporal regulation of outer kinetochore assembly is essential for accurate cell division. The Rockefeller University Press 2013-04-01 /pmc/articles/PMC3613690/ /pubmed/23530067 http://dx.doi.org/10.1083/jcb.201301006 Text en © 2013 Gascoigne and Cheeseman This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Gascoigne, Karen E. Cheeseman, Iain M. CDK-dependent phosphorylation and nuclear exclusion coordinately control kinetochore assembly state |
title | CDK-dependent phosphorylation and nuclear exclusion coordinately control kinetochore assembly state |
title_full | CDK-dependent phosphorylation and nuclear exclusion coordinately control kinetochore assembly state |
title_fullStr | CDK-dependent phosphorylation and nuclear exclusion coordinately control kinetochore assembly state |
title_full_unstemmed | CDK-dependent phosphorylation and nuclear exclusion coordinately control kinetochore assembly state |
title_short | CDK-dependent phosphorylation and nuclear exclusion coordinately control kinetochore assembly state |
title_sort | cdk-dependent phosphorylation and nuclear exclusion coordinately control kinetochore assembly state |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3613690/ https://www.ncbi.nlm.nih.gov/pubmed/23530067 http://dx.doi.org/10.1083/jcb.201301006 |
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