CDK-regulated dimerization of M18BP1 on a Mis18 hexamer is necessary for CENP-A loading
- Max Planck Institute of Molecular Physiology, Germany
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 Yippie 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.
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Author details
Funding
European Research Council (AdG 669686 RECEPIANCE)
- Andrea Musacchio
Deutsche Forschungsgemeinschaft (Collaborative Research Centre (CRC) 1093)
- Andrea Musacchio
Alexander von Humboldt-Stiftung (Postdoctoral fellowship)
- Dongqing Pan
Alexander von Humboldt-Stiftung (Postdoctoral fellowship)
- Priyanka Singh
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Pan et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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CDK-regulated dimerization of M18BP1 on a Mis18 hexamer is necessary for CENP-A loading
eLife 6:e23352.
https://doi.org/10.7554/eLife.23352
