Topoisomerase VI is a chirally-selective, preferential DNA decatenase

  1. Shannon J McKie
  2. Parth Desai
  3. Yeonee Seol
  4. Adam MB Allen
  5. Anthony Maxwell  Is a corresponding author
  6. Keir C Neuman  Is a corresponding author
  1. National Heart, Lung and Blood Institute, National Institutes of Health, United States
  2. John Innes Centre, United Kingdom

Abstract

DNA topoisomerase VI (topo VI) is a type IIB DNA topoisomerase found predominantly in archaea and some bacteria, but also in plants and algae. Since its discovery, topo VI has been proposed to be a DNA decatenase, however robust evidence and a mechanism for its preferential decatenation activity was lacking. Using single-molecule magnetic tweezers measurements and supporting ensemble biochemistry, we demonstrate that Methanosarcina mazei topo VI preferentially unlinks, or decatenates DNA crossings, in comparison to relaxing supercoils, through a preference for certain DNA crossing geometries. In addition, topo VI demonstrates a significant increase in ATPase activity, DNA binding and rate of strand passage, with increasing DNA writhe, providing further evidence that topo VI is a DNA crossing sensor. Our study strongly suggests that topo VI has evolved an intrinsic preference for the unknotting and decatenation of interlinked chromosomes by sensing and preferentially unlinking DNA crossings with geometries close to 90°.

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Article and author information

Author details

  1. Shannon J McKie

    Laboratory of Single Molecule Biophysics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Parth Desai

    Laboratory of Single Molecule Biophysics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Yeonee Seol

    Laboratory of Single Molecule Biophysics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Adam MB Allen

    Department of Biochemistry and Metabolism, John Innes Centre, Norwich, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Anthony Maxwell

    Department of Biochemistry and Metabolism, John Innes Centre, Norwich, United Kingdom
    For correspondence
    tony.maxwell@jic.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
  6. Keir C Neuman

    Laboratory of Single Molecule Biophysics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, United States
    For correspondence
    neumankc@nhlbi.nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0863-5671

Funding

National Institutes of Health (1ZIAHL001056)

  • Shannon J McKie
  • Parth Desai
  • Yeonee Seol

Wellcome Trust

  • Shannon J McKie

Biotechnology and Biological Sciences Research Council (BB/P012523/1)

  • Anthony Maxwell

Wellcome Trust (110072/Z/15/Z)

  • Anthony Maxwell

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: January 29, 2021
  2. Preprint posted: February 16, 2021 (view preprint)
  3. Accepted: January 24, 2022
  4. Accepted Manuscript published: January 25, 2022 (version 1)
  5. Version of Record published: February 11, 2022 (version 2)

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

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  1. Shannon J McKie
  2. Parth Desai
  3. Yeonee Seol
  4. Adam MB Allen
  5. Anthony Maxwell
  6. Keir C Neuman
(2022)
Topoisomerase VI is a chirally-selective, preferential DNA decatenase
eLife 11:e67021.
https://doi.org/10.7554/eLife.67021
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