Polo-like Kinase 1 Licenses CENP-A Deposition at Centromeres
Name
Cheeseman_Polo-like kinase.pdf
Size
1.38 MB
Format
Adobe PDF
Checksum (MD5)
8cc3135015facf035a42b2736cc23c4b
Author(s)
McKinley, Kara Lavidge
Cheeseman, Iain M
Date Issued
July 2014
Journal
Cell
Publisher
Elsevier
Citation
McKinley, Kara L., and Iain M. Cheeseman. “Polo-like Kinase 1 Licenses CENP-A Deposition at Centromeres.” Cell 158.2 (2014): 397–411.
Version
Author's final manuscript
Abstract
To ensure the stable transmission of the genome during vertebrate cell division, the mitotic spindle must attach to a single locus on each chromosome, termed the centromere. The fundamental requirement for faithful centromere inheritance is the controlled deposition of the centromere-specifying histone, CENP-A. However, the regulatory mechanisms that ensure the precise control of CENP-A deposition have proven elusive. Here, we identify polo-like kinase 1 (Plk1) as a centromere-localized regulator required to initiate CENP-A deposition in human cells. We demonstrate that faithful CENP-A deposition requires integrated signals from Plk1 and cyclin-dependent kinase (CDK), with Plk1 promoting the localization of the key CENP-A deposition factor, the Mis18 complex, and CDK inhibiting Mis18 complex assembly. By bypassing these regulated steps, we uncoupled CENP-A deposition from cell-cycle progression, resulting in mitotic defects. Thus, CENP-A deposition is controlled by a two-step regulatory paradigm comprised of Plk1 and CDK that is crucial for genomic integrity.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/j.cell.2014.06.016
