ArticleNature2010
A novel and unified two-metal mechanism for DNA cleavage by type II and IA topoisomerases.
Article in Nature, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers.
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Who cites it
114 citing papers in PubMed, 176 citations in OpenAlex.
- Networked salt-bridges mediate magnesium-dependent conformational dynamics and functional regulation in type IA topoisomerases.Nature communications · 2026Article
- Dimerization of thebioRxiv : the preprint server for biology · 2026Article
- Direct trapping of the transport-segment DNA by the central domain of type IIA topoisomerases.Science advances · 2025Article
- Mechanism of Action of Gepotidacin: Well-Balanced Dual-Targeting againstACS infectious diseases · 2025Article
- Structural Mechanisms of Topoisomerase-Targeting Drugs.Annual review of biochemistry · 2025Review
- Article
- Structural insights into human topoisomerase 3β DNA and RNA catalysis and nucleic acid gate dynamics.Nature communications · 2025Article
- Topoisomerase II N-terminal ATPase Clamp Stabilization.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Topoisomerase II Inhibition in Cancer: A Focus on Metal Complexes.Mini reviews in medicinal chemistry · 2025Review
- Cryo-EM structures of the Spo11 core complex bound to DNA.Nature structural & molecular biology · 2025Article
- How Do Gepotidacin and Zoliflodacin Stabilize DNA-Cleavage Complexes with Bacterial Type IIA Topoisomerases? 2. A Single Moving Metal Mechanism.International journal of molecular sciences · 2024Article
- Structural basis of chiral wrap and T-segment capture byProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Reconstitution of SPO11-dependent double-strand break formation.bioRxiv : the preprint server for biology · 2024Article
- How Do Gepotidacin and Zoliflodacin Stabilize DNA Cleavage Complexes with Bacterial Type IIA Topoisomerases? 1. Experimental Definition of Metal Binding Sites.International journal of molecular sciences · 2024Article
- Structural basis for difunctional mechanism of m-AMSA against African swine fever virus pP1192R.Nucleic acids research · 2024Article
- Structural and functional insights into the T-even type bacteriophage topoisomerase II.Nature communications · 2024Article
- Experimental localization of metal-binding sites reveals the role of metal ions in type II DNA topoisomerases.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Structural insights into the DNA topoisomerase II of the African swine fever virus.Nature communications · 2024Article
- Gyrase and Topoisomerase IV: Recycling Old Targets for New Antibacterials to Combat Fluoroquinolone Resistance.ACS infectious diseases · 2024Review
- Variation of Structure and Cellular Functions of Type IA Topoisomerases across the Tree of Life.Cells · 2024Review
54 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Type II topoisomerases are required for the management of DNA tangles and supercoils, and are targets of clinical antibiotics and anti-cancer agents. These enzymes catalyse the ATP-dependent passage of one DNA duplex (the transport or T-segment) through a transient, double-stranded break in another (the gate or G-segment), navigating DNA through the protein using a set of dissociable internal interfaces, or 'gates'. For more than 20 years, it has been established that a pair of dimer-related tyrosines, together with divalent cations, catalyse G-segment cleavage. Recent efforts have proposed that strand scission relies on a 'two-metal mechanism', a ubiquitous biochemical strategy that supports vital cellular processes ranging from DNA synthesis to RNA self-splicing. Here we present the structure of the DNA-binding and cleavage core of Saccharomyces cerevisiae topoisomerase II covalently linked to DNA through its active-site tyrosine at 2.5A resolution, revealing for the first time the organization of a cleavage-competent type II topoisomerase configuration. Unexpectedly, metal-soaking experiments indicate that cleavage is catalysed by a novel variation of the classic two-metal approach. Comparative analyses extend this scheme to explain how distantly-related type IA topoisomerases cleave single-stranded DNA, unifying the cleavage mechanisms for these two essential enzyme families. The structure also highlights a hitherto undiscovered allosteric relay that actuates a molecular 'trapdoor' to prevent subunit dissociation during cleavage. This connection illustrates how an indispensable chromosome-disentangling machine auto-regulates DNA breakage to prevent the aberrant formation of mutagenic and cytotoxic genomic lesions.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.