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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...

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Detalles Bibliográficos
Autores principales: Gascoigne, Karen E., Cheeseman, Iain M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2013
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.
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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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