Structural snapshots of Xer recombination reveal activation by synaptic complex remodeling and DNA bending

  1. Aleksandra Bebel
  2. Ezgi Karaca
  3. Banushree Kumar
  4. W Marshall Stark
  5. Orsolya Barabas  Is a corresponding author
  1. European Molecular Biology Laboratory, Germany
  2. University of Glasgow, United Kingdom

Abstract

Bacterial Xer site-specific recombinases play an essential genome maintenance role by unlinking chromosome multimers, but their mechanism of action has remained structurally uncharacterized. Here, we present two high-resolution structures of Helicobacter pylori XerH with its recombination site DNA difH, representing pre-cleavage and post-cleavage synaptic intermediates in the recombination pathway. The structures reveal that activation of DNA strand cleavage and rejoining involves large conformational changes and DNA bending, suggesting how interaction with the cell division protein FtsK may license recombination at the septum. Together with biochemical and in vivo analysis, our structures also reveal how a small sequence asymmetry in difH defines protein conformation in the synaptic complex and orchestrates the order of DNA strand exchanges. Our results provide insights into the catalytic mechanism of Xer recombination and a model for regulation of recombination activity during cell division.

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Author details

  1. Aleksandra Bebel

    Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Ezgi Karaca

    Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Banushree Kumar

    Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. W Marshall Stark

    Institute of Molecular, Cell and Systems Biology, University of Glasgow, Glasgow, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Orsolya Barabas

    Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany
    For correspondence
    barabas@embl.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2873-5872

Funding

European Molecular Biology Laboratory (Intramural Funds)

  • Aleksandra Bebel
  • Ezgi Karaca
  • Banushree Kumar
  • Orsolya Barabas

Alexander von Humboldt-Stiftung (Postdoctoral Fellowship)

  • Ezgi Karaca

EMBL International PhD Programme (Graduate Student Fellowship)

  • Aleksandra Bebel

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

Reviewing Editor

  1. James M Berger, Johns Hopkins University School of Medicine, United States

Publication history

  1. Received: July 15, 2016
  2. Accepted: December 21, 2016
  3. Accepted Manuscript published: December 23, 2016 (version 1)
  4. Version of Record published: January 17, 2017 (version 2)

Copyright

© 2016, Bebel 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. Aleksandra Bebel
  2. Ezgi Karaca
  3. Banushree Kumar
  4. W Marshall Stark
  5. Orsolya Barabas
(2016)
Structural snapshots of Xer recombination reveal activation by synaptic complex remodeling and DNA bending
eLife 5:e19706.
https://doi.org/10.7554/eLife.19706
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