Scc2/Nipbl hops between chromosomal cohesin rings after loading

  1. James DP Rhodes
  2. Davide Mazza
  3. Kim A Nasmyth
  4. Stephan Uphoff  Is a corresponding author
  1. University of Oxford, United Kingdom
  2. Istituto Scientifico Ospedale San Raffaele, Italy

Abstract

The cohesin complex mediates DNA-DNA interactions both between (sister chromatid cohesion) and within chromosomes (DNA looping). It has been suggested that intra-chromosome loops are generated by extrusion of DNAs through the lumen of cohesin's ring. Scc2 (Nipbl) stimulates cohesin's ABC-like ATPase and is essential for loading cohesin onto chromosomes. However, it is possible that the stimulation of cohesin's ATPase by Scc2 also has a post-loading function, for example driving loop extrusion. Using fluorescence recovery after photobleaching (FRAP) and single- molecule tracking, we show that Scc2 binds dynamically to chromatin, principally through an association with cohesin. Scc2's movement within chromatin is consistent with a 'stop-and-go' or 'hopping' motion. We suggest that a low diffusion coefficient, a low stoichiometry relative to cohesin, and a high affinity for chromosomal cohesin enables Scc2 to move rapidly from one chromosomal cohesin complex to another, performing a function distinct from loading.

Article and author information

Author details

  1. James DP Rhodes

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Davide Mazza

    Centro di Imaging Sperimentale, Istituto Scientifico Ospedale San Raffaele, Milano, Italy
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2776-4142
  3. Kim A Nasmyth

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7030-4403
  4. Stephan Uphoff

    Department of Biochemistry, University of Oxford, Oxford, United Kingdom
    For correspondence
    stephan.uphoff@bioch.ox.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3579-0888

Funding

Wellcome (091859/Z/10/Z)

  • Kim A Nasmyth

H2020 European Research Council (294401)

  • Kim A Nasmyth

Cancer Research UK (C573/A12386)

  • Kim A Nasmyth

Wellcome (101636/Z/13/Z)

  • Stephan Uphoff

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

Reviewing Editor

  1. Andrea Musacchio, Max Planck Institute of Molecular Physiology, Germany

Publication history

  1. Received: June 28, 2017
  2. Accepted: September 8, 2017
  3. Accepted Manuscript published: September 15, 2017 (version 1)
  4. Version of Record published: September 29, 2017 (version 2)

Copyright

© 2017, Rhodes 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. James DP Rhodes
  2. Davide Mazza
  3. Kim A Nasmyth
  4. Stephan Uphoff
(2017)
Scc2/Nipbl hops between chromosomal cohesin rings after loading
eLife 6:e30000.
https://doi.org/10.7554/eLife.30000

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