1. Structural Biology and Molecular Biophysics
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Architecture of the chromatin remodeler RSC and insights into its nucleosome engagement

  1. Avinash B Patel  Is a corresponding author
  2. Camille M Moore
  3. Basil J Greber
  4. Jie Luo
  5. Stefan A Zukin
  6. Jeff Ranish
  7. Eva Nogales  Is a corresponding author
  1. University of California, Berkeley, United States
  2. The Institute for Systems Biology, United States
  3. Lawrence Berkeley National Laboratory, United States
Research Article
  • Cited 10
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Cite this article as: eLife 2019;8:e54449 doi: 10.7554/eLife.54449

Abstract

Eukaryotic DNA is packaged into nucleosome arrays, which are repositioned by chromatin remodeling complexes to control DNA accessibility. The Saccharomyces cerevisiae RSC (Remodeling the Structure of Chromatin) complex, a member of the SWI/SNF chromatin remodeler family, plays critical roles in genome maintenance, transcription, and DNA repair. Here we report cryo-electron microscopy (cryo-EM) and crosslinking mass spectrometry (CLMS) studies of yeast RSC complex and show that RSC is composed of a rigid tripartite core and two flexible lobes. The core structure is scaffolded by an asymmetric Rsc8 dimer and built with the evolutionarily conserved subunits Sfh1, Rsc6, Rsc9 and Sth1. The flexible ATPase lobe, composed of helicase subunit Sth1, Arp7, Arp9 and Rtt102, is anchored to this core by the N-terminus of Sth1. Our cryo-EM analysis of RSC bound to a nucleosome core particle shows that in addition to the expected nucleosome-Sth1 interactions, RSC engages histones and nucleosomal DNA through one arm of the core structure, composed of the Rsc8 SWIRM domains, Sfh1 and Npl6. Our findings provide structural insights into the conserved assembly process for all members of the SWI/SNF family of remodelers, and illustrate how RSC selects, engages, and remodels nucleosomes.

Article and author information

Author details

  1. Avinash B Patel

    Biophysics Graduate Group, University of California, Berkeley, Berkeley, United States
    For correspondence
    patelab@berkeley.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9140-8375
  2. Camille M Moore

    Molecular and Cell Biology Department, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Basil J Greber

    California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9379-7159
  4. Jie Luo

    The Institute for Systems Biology, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Stefan A Zukin

    Chemistry Department, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Jeff Ranish

    The Institute for Systems Biology, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Eva Nogales

    Molecular Biophysics and Integrative Bio-Imaging Division, Lawrence Berkeley National Laboratory, Berkeley, United States
    For correspondence
    enogales@lbl.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9816-3681

Funding

National Institutes of Health (U24GM129547)

  • Eva Nogales

National Institute of General Medical Sciences (R01-GM63072)

  • Eva Nogales

National Institute of General Medical Sciences (R35-GM127018)

  • Eva Nogales

National Institute of General Medical Sciences (R01- GM110064)

  • Jeff Ranish

National Institute of General Medical Sciences (R01-HL133678)

  • Jeff Ranish

Howard Hughes Medical Institute

  • Eva Nogales

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

Reviewing Editor

  1. Cynthia Wolberger, Johns Hopkins University School of Medicine, United States

Publication history

  1. Received: December 16, 2019
  2. Accepted: December 23, 2019
  3. Accepted Manuscript published: December 30, 2019 (version 1)
  4. Version of Record published: January 14, 2020 (version 2)

Copyright

© 2019, Patel 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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