Polo-like Kinase 1 Licenses CENP-A Deposition at Centromeres
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 hist...
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| Format: | Article |
| Language: | en_US |
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Elsevier
2017
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| Online Access: | http://hdl.handle.net/1721.1/106982 https://orcid.org/0000-0001-6283-9168 https://orcid.org/0000-0002-3829-5612 |
| _version_ | 1826200492793921536 |
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| author | McKinley, Kara Lavidge Cheeseman, Iain M |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology McKinley, Kara Lavidge Cheeseman, Iain M |
| author_sort | McKinley, Kara Lavidge |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:37:00Z |
| format | Article |
| id | mit-1721.1/106982 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:37:00Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1069822022-09-27T20:47:55Z Polo-like Kinase 1 Licenses CENP-A Deposition at Centromeres McKinley, Kara Lavidge Cheeseman, Iain M Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research McKinley, Kara Lavidge Cheeseman, Iain M 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. Leukemia & Lymphoma Society of America (Scholar Award) National Institute of General Medical Sciences (U.S.) (Grant GM088313) American Cancer Society (Research Scholar Grant 121776) 2017-02-16T21:50:35Z 2017-02-16T21:50:35Z 2014-07 2014-03 Article http://purl.org/eprint/type/JournalArticle 0092-8674 1097-4172 http://hdl.handle.net/1721.1/106982 McKinley, Kara L., and Iain M. Cheeseman. “Polo-like Kinase 1 Licenses CENP-A Deposition at Centromeres.” Cell 158.2 (2014): 397–411. https://orcid.org/0000-0001-6283-9168 https://orcid.org/0000-0002-3829-5612 en_US http://dx.doi.org/10.1016/j.cell.2014.06.016 Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | McKinley, Kara Lavidge Cheeseman, Iain M Polo-like Kinase 1 Licenses CENP-A Deposition at Centromeres |
| title | Polo-like Kinase 1 Licenses CENP-A Deposition at Centromeres |
| title_full | Polo-like Kinase 1 Licenses CENP-A Deposition at Centromeres |
| title_fullStr | Polo-like Kinase 1 Licenses CENP-A Deposition at Centromeres |
| title_full_unstemmed | Polo-like Kinase 1 Licenses CENP-A Deposition at Centromeres |
| title_short | Polo-like Kinase 1 Licenses CENP-A Deposition at Centromeres |
| title_sort | polo like kinase 1 licenses cenp a deposition at centromeres |
| url | http://hdl.handle.net/1721.1/106982 https://orcid.org/0000-0001-6283-9168 https://orcid.org/0000-0002-3829-5612 |
| work_keys_str_mv | AT mckinleykaralavidge pololikekinase1licensescenpadepositionatcentromeres AT cheesemaniainm pololikekinase1licensescenpadepositionatcentromeres |