1. Structural Biology and Molecular Biophysics
  2. Chromosomes and Gene Expression

Decoding the centromeric nucleosome through CENP-N

  1. Satyakrishna Pentakota
  2. Keda Zhou
  3. Charlotte Smith
  4. Stefano Maffini
  5. Arsen Petrovic
  6. Garry P Morgan
  7. John R Weir
  8. Ingrid R Vetter
  9. Andrea Musacchio  Is a corresponding author
  10. Karolin Luger  Is a corresponding author
  1. Max Planck Institute of Molecular Physiology, Germany
  2. University of Colorado, Boulder, United States
https://doi.org/10.7554/eLife.33442
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Cite this article
  1. Satyakrishna Pentakota
  2. Keda Zhou
  3. Charlotte Smith
  4. Stefano Maffini
  5. Arsen Petrovic
  6. Garry P Morgan
  7. John R Weir
  8. Ingrid R Vetter
  9. Andrea Musacchio
  10. Karolin Luger
(2017)
Decoding the centromeric nucleosome through CENP-N
eLife 6:e33442.
https://doi.org/10.7554/eLife.33442
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Abstract

Centromere protein (CENP) A, a histone H3 variant, is a key epigenetic determinant of chromosome domains known as centromeres. Centromeres nucleate kinetochores, multi-subunit complexes that capture spindle microtubules to promote chromosome segregation during mitosis. Two kinetochore proteins, CENP-C and CENP-N, recognize CENP-A in the context of a rare CENP-A nucleosome. Here, we reveal the structural basis for the exquisite selectivity of CENP-N for centromeres. CENP-N uses charge and space complementarity to decode the L1 loop that is unique to CENP-A. It also engages in extensive interactions with a 15-base pair segment of the distorted nucleosomal DNA double helix, in a position predicted to exclude chromatin remodelling enzymes. Besides CENP-A, stable centromere recruitment of CENP-N requires a coincident interaction with a newly identified binding motif on nucleosome-bound CENP-C. Collectively, our studies clarify how CENP-N and CENP-C decode and stabilize the non-canonical CENP-A nucleosome to enforce epigenetic centromere specification and kinetochore assembly.

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Author details

  1. Satyakrishna Pentakota

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

  2. Keda Zhou

    Department of Chemistry and Biochemistry, University of Colorado, Boulder, Boulder, United States
    Competing interests
    No competing interests declared.

  3. Charlotte Smith

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

  4. Stefano Maffini

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

  5. Arsen Petrovic

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

  6. Garry P Morgan

    Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Boulder, United States
    Competing interests
    No competing interests declared.

  7. John R Weir

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

  8. Ingrid R Vetter

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

  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, Senior Editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2362-8784

  10. Karolin Luger

    Department of Chemistry and Biochemistry, University of Colorado, Boulder, Boulder, United States
    For correspondence
    karolin.luger@colorado.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5136-5331

Funding

H2020 European Research Council (AdG 669686)

  • Andrea Musacchio

Deutsche Forschungsgemeinschaft (CRC1093)

  • Andrea Musacchio

National Institutes of Health (GM067777)

  • Karolin Luger

Howard Hughes Medical Institute

  • Karolin Luger

Max-Planck-Gesellschaft (Open-access funding)

  • Andrea Musacchio

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Geeta J Narlikar, University of California, San Francisco, United States

Version history

  1. Received: November 8, 2017
  2. Accepted: December 23, 2017
  3. Accepted Manuscript published: December 27, 2017 (version 1)
  4. Version of Record published: January 22, 2018 (version 2)

Copyright

© 2017, Pentakota 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. Satyakrishna Pentakota
  2. Keda Zhou
  3. Charlotte Smith
  4. Stefano Maffini
  5. Arsen Petrovic
  6. Garry P Morgan
  7. John R Weir
  8. Ingrid R Vetter
  9. Andrea Musacchio
  10. Karolin Luger
(2017)
Decoding the centromeric nucleosome through CENP-N
eLife 6:e33442.
https://doi.org/10.7554/eLife.33442

Share this article

https://doi.org/10.7554/eLife.33442

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