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

  1. Dongqing Pan
  2. Kerstin Klare
  3. Arsen Petrovic
  4. Annika Take
  5. Kai Walstein
  6. Priyanka Singh
  7. Arnaud Rondelet
  8. Alex W Bird
  9. Andrea Musacchio  Is a corresponding author
  1. Max-Planck Institute of Molecular Physiology, Germany
  2. 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.

Article and author information

Author details

  1. Dongqing Pan

    Department of Mechanistic Cell Biology, Max-Planck Institute of Molecular Physiology, Dortmund, Germany
    Competing interests
    No competing interests declared.
  2. Kerstin Klare

    Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    Competing interests
    No competing interests declared.
  3. Arsen Petrovic

    Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    Competing interests
    No competing interests declared.
  4. Annika Take

    Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    Competing interests
    No competing interests declared.
  5. Kai Walstein

    Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    Competing interests
    No competing interests declared.
  6. Priyanka Singh

    Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    Competing interests
    No competing interests declared.
  7. Arnaud Rondelet

    Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5816-4137
  8. Alex W Bird

    Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1061-0799
  9. Andrea Musacchio

    Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    For correspondence
    andrea.musacchio@mpi-dortmund.mpg.de
    Competing interests
    Andrea Musacchio, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2362-8784

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.

Reviewing Editor

  1. Asifa Akhtar, Max Planck Institute for Immunobiology and Epigenetics, Germany

Version history

  1. Received: November 16, 2016
  2. Accepted: December 19, 2016
  3. Accepted Manuscript published: January 6, 2017 (version 1)
  4. Accepted Manuscript updated: January 9, 2017 (version 2)
  5. Version of Record published: January 19, 2017 (version 3)
  6. Version of Record updated: January 25, 2017 (version 4)

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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  1. Dongqing Pan
  2. Kerstin Klare
  3. Arsen Petrovic
  4. Annika Take
  5. Kai Walstein
  6. Priyanka Singh
  7. Arnaud Rondelet
  8. Alex W Bird
  9. Andrea Musacchio
(2017)
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

Share this article

https://doi.org/10.7554/eLife.23352

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