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Cited by 9Cancer therapeutics and mechanismsEnzyme Structure and FunctionDNA and Nucleic Acid Chemistry

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Structures of topoisomerase V in complex with DNA reveal unusual DNA-binding mode and novel relaxation mechanism

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Osterman, Amy, Mondragón, Alfonso·2022·eLife
DOI 10.7554/elife.72702PMC PMC9489208

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Abstract

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 3 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.

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Metadata

Authors
Osterman, A., & Mondragón, A.
Affiliations
Northwestern University (US)
Corresponding author
Mondragón, Alfonso
ORCID
Mondragón, Alfonso
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2022-08-15
Volume
11
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.72702
PMC
PMC9489208
OpenAlex
W4291605614
Cited by
9
References
2
Citations by year
2026: 3 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 1
FWCI
0.49
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institute of General Medical Sciences (R35-GM118108)
  • National Cancer Institute (P30-CA060553)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer therapeutics and mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
Keywords
DNA relaxation, DNA binding modes, processivity factor, DNA bending, protein-DNA complex structure, DNA repair
MeSH terms
DNA, DNA Topoisomerases, Type I, Euryarchaeota, DNA-(Apurinic or Apyrimidinic Site) Lyase

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