CDK-regulated dimerization of M18BP1 on a Mis18 hexamer is necessary for CENP-A loading

eLife

Andrea Musacchio¹  Alexander W Bird¹  Dongqing Pan¹  Arsen Petrovic¹  Annika Take¹  Arnaud Rondelet¹  Kerstin Klare¹  Kai Walstein¹  Priyanka Singh¹ 

[1] Department of Mechanistic Cell Biology, Max-Planck Institute of Molecular Physiology, Dortmund, Germany;

关键词: kinetochore;    centromere;    cell cycle;    CENP-A;    chromatin;   

DOI  :  10.7554/eLife.23352

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown