{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["McKinley KL"],"funding":["NIGMS NIH HHS"],"pagination":["397-411"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC4192726"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["158(2)"],"pubmed_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."],"journal":["Cell"],"pubmed_title":["Polo-like kinase 1 licenses CENP-A deposition at centromeres."],"pmcid":["PMC4192726"],"funding_grant_id":["GM088313","T32 GM007287","R01 GM088313"],"pubmed_authors":["McKinley KL","Cheeseman IM"],"additional_accession":[]},"is_claimable":false,"name":"Polo-like kinase 1 licenses CENP-A deposition at centromeres.","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.","dates":{"release":"2014-01-01T00:00:00Z","publication":"2014 Jul","modification":"2024-10-19T12:20:24.788Z","creation":"2019-03-27T01:37:25Z"},"accession":"S-EPMC4192726","cross_references":{"pubmed":["25036634"],"doi":["10.1016/j.cell.2014.06.016"]}}