CDK-dependent phosphorylation and nuclear exclusion coordinately control kinetochore assembly state
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Gascoigne-2013-CDK-dependent phosph.pdf
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3.39 MB
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8076757b60114f64f5558c3d887805bc
Author(s)
Gascoigne, Karen E.
Cheeseman, Iain M
Date Issued
March 2013
Journal
The Journal of Cell Biology
Publisher
Rockefeller University Press, The
Citation
Gascoigne, K. E., and I. M. Cheeseman. “CDK-dependent phosphorylation and nuclear exclusion coordinately control kinetochore assembly state.” The Journal of Cell Biology 201, no. 1 (April 1, 2013): 23-32.
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Creative Commons Attribution Non-Commercial
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DOI of Published Version
https://doi.org/10.1083/jcb.201301006
