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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 Mis18?:Mis18? 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 Mis18?:Mis18? 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 Mis18?:Mis18?, 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 Mis18?:Mis18? scaffold.

SUBMITTER: Pan D 

PROVIDER: S-EPMC5245964 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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

Pan Dongqing D   Klare Kerstin K   Petrovic Arsen A   Take Annika A   Walstein Kai K   Singh Priyanka P   Rondelet Arnaud A   Bird Alexander W AW   Musacchio Andrea A  

eLife 20170106


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 C  ...[more]

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