Structures of topoisomerase V in complex with DNA reveal unusual DNA binding mode and novel relaxation mechanism
Topoisomerase V is a unique topoisomerase that combines DNA repair and topoisomerase activities. The enzyme has an unusual arrangement, with a small topoisomerase domain followed by 12 tandem (HhH)2 domains, which include three AP lyase repair domains. The uncommon architecture of this enzyme bears no resemblance to any other known topoisomerase. Here we present structures of topoisomerase V in complex with DNA. The structures show that the (HhH)2 domains wrap around the DNA and in this manner appear to act as a processivity factor. There is a conformational change in the protein to expose the topoisomerase active site. The DNA bends sharply to enter the active site, which melts the DNA and probably facilitates relaxation. The structures show a DNA binding mode not observed before and provide information on the way this atypical topoisomerase relaxes DNA. In common with type IB enzymes, topoisomerase V relaxes DNA using a controlled rotation mechanism, but the structures show that topoisomerase V accomplishes this in different manner. Overall, the structures firmly establish that type IC topoisomerases form a distinct type of topoisomerases, with no similarities to other types at the sequence, structural, or mechanistic level. They represent a completely different solution to DNA relaxation.
Atomic coordinates and structure factors for the reported crystal structures have been deposited with the Protein Data Bank under the accession numbers 8DF7, 8DF8, 8DF9, and 8DFB.
Article and author information
National Institute of General Medical Sciences (R35-GM118108)
- Alfonso Mondragón
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- James M Berger, Johns Hopkins University, United States
- Received: August 1, 2021
- Preprint posted: August 20, 2021 (view preprint)
- Accepted: August 14, 2022
- Accepted Manuscript published: August 15, 2022 (version 1)
- Version of Record published: September 20, 2022 (version 2)
© 2022, Osterman & Mondragón
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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