Topoisomerase VI is a chirally-selective, preferential DNA decatenase
- National Heart, Lung and Blood Institute, National Institutes of Health, United States
- 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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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.
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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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Topoisomerase VI is a chirally-selective, preferential DNA decatenase
eLife 11:e67021.
https://doi.org/10.7554/eLife.67021
