title: CDK-regulated dimerization of M18BP1 on a Mis18 hexamer is necessary for CENP-A loading.
abstract: Centromeres are unique chromosomal loci that promote the assembly of kinetochores, macromolecular complexes that bind spindle microtubules during mitosis. In most organisms, centromeres lack defined genetic features. Rather, they are specified epigenetically by a centromere-specific histone H3 variant, CENP-A. The Mis18 complex, comprising the Mis18α:Mis18β subcomplex and M18BP1, is crucial for CENP-A homeostasis. It recruits the CENP-A-specific chaperone HJURP to centromeres and primes it for CENP-A loading. We report here that a specific arrangement of Yippee domains in a human Mis18α:Mis18β 4:2 hexamer binds two copies of M18BP1 through M18BP1's 140 N-terminal residues. Phosphorylation by Cyclin-dependent kinase 1 (CDK1) at two conserved sites in this region destabilizes binding to Mis18α:Mis18β, limiting complex formation to the G1 phase of the cell cycle. Using an improved viral 2A peptide co-expression strategy, we demonstrate that CDK1 controls Mis18 complex recruitment to centromeres by regulating oligomerization of M18BP1 through the Mis18α:Mis18β scaffold.
authors.affiliation: Department of Mechanistic Cell Biology, Max-Planck Institute of Molecular Physiology, Dortmund, Germany.
authors.forename: Dongqing
authors.initials: D
authors.lastname: Pan
authors.affiliation: Department of Mechanistic Cell Biology, Max-Planck Institute of Molecular Physiology, Dortmund, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Klare
authors.affiliation: Department of Mechanistic Cell Biology, Max-Planck Institute of Molecular Physiology, Dortmund, Germany.
authors.forename: Arsen
authors.initials: A
authors.lastname: Petrovic
authors.affiliation: Department of Mechanistic Cell Biology, Max-Planck Institute of Molecular Physiology, Dortmund, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Take
authors.affiliation: Department of Mechanistic Cell Biology, Max-Planck Institute of Molecular Physiology, Dortmund, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Walstein
authors.affiliation: Department of Mechanistic Cell Biology, Max-Planck Institute of Molecular Physiology, Dortmund, Germany.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Singh
authors.affiliation: Department of Mechanistic Cell Biology, Max-Planck Institute of Molecular Physiology, Dortmund, Germany.
authors.forename: Arnaud
authors.identifier: 0000-0001-5816-4137
authors.initials: A
authors.lastname: Rondelet
authors.affiliation: Department of Mechanistic Cell Biology, Max-Planck Institute of Molecular Physiology, Dortmund, Germany.
authors.forename: Alexander W
authors.identifier: 0000-0002-1061-0799
authors.initials: AW
authors.lastname: Bird
authors.affiliation: Department of Mechanistic Cell Biology, Max-Planck Institute of Molecular Physiology, Dortmund, Germany.|Centre for Medical Biotechnology, Faculty of Biology, University Duisburg-Essen, Essen, Germany.
authors.forename: Andrea
authors.identifier: 0000-0003-2362-8784
authors.initials: A
authors.lastname: Musacchio
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002503:Centromere / Q000378:metabolism; D000076247:Centromere Protein A / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D011485:Protein Binding; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; C502942:MIS18A protein, human; C517147:MIS18BP1 protein, human; C517146:OIP5 protein, human; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human
keywords: CENP-A; biochemistry; cell biology; cell cycle; centromere; chromatin; human; kinetochore