CDK-regulated dimerization of M18BP1 on a Mis18 hexamer is necessary for CENP-A loading
| Autor: | Alexander W. Bird, Andrea Musacchio, Arnaud Rondelet, Annika Take, Kerstin Klare, Dongqing Pan, Kai Walstein, Priyanka Singh, Arsen Petrovic |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Chromosomal Proteins Non-Histone QH301-705.5 Science Forschungszentren » Zentrum für Medizinische Biotechnologie (ZMB) Fakultät für Biologie Cell Cycle Proteins macromolecular substances Random hexamer Biochemistry General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Cyclin-dependent kinase Centromere Protein A ddc:570 CDC2 Protein Kinase Centromere Humans Phosphorylation Biology (General) Mitosis Adaptor Proteins Signal Transducing General Immunology and Microbiology biology Kinetochore General Neuroscience Cell Biology General Medicine Cell biology Chromatin Spindle apparatus kinetochore ddc:57 030104 developmental biology centromere biology.protein chromatin Medicine cell cycle Protein Multimerization Protein Processing Post-Translational CENP-A Biologie Research Article Human Protein Binding |
| Zdroj: | eLife, Vol 6 (2017) eLife |
| Popis: | 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. DOI: http://dx.doi.org/10.7554/eLife.23352.001 |
| Databáze: | OpenAIRE |
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