title: Polo-like kinase 1 licenses CENP-A deposition at centromeres.
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.
authors.affiliation: Whitehead Institute and Department of Biology, MIT, Nine Cambridge Center, Cambridge, MA 02142, USA.
authors.forename: Kara L
authors.initials: KL
authors.lastname: McKinley
authors.affiliation: Whitehead Institute and Department of Biology, MIT, Nine Cambridge Center, Cambridge, MA 02142, USA. Electronic address: icheese@wi.mit.edu.
authors.forename: Iain M
authors.initials: IM
authors.lastname: Cheeseman
mesh_terms: D001324:Autoantigens / Q000378:metabolism*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D002503:Centromere / Q000378:metabolism*; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D042822:Genomic Instability; D006367:HeLa Cells; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
chemical_list: D001324:Autoantigens; D018797:Cell Cycle Proteins; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; D018844:Cyclin-Dependent Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C000619700:CENPA protein, human