ArticleProceedings of the National Academy of Sciences of the United States of America2012
DNA cleavage and opening reactions of human topoisomerase IIα are regulated via Mg2+-mediated dynamic bending of gate-DNA.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed.
- Complex mechanisms of topoisomerase II poisons revealed by whole-genome analysis.Communications biology · 2026Article
- Mutagenesis of Intrinsically Disordered Domain Impacts Topoisomerase IIα Catalytic Activity.International journal of molecular sciences · 2025Article
- Single-molecule FRET-based approach for protein-targeted drug discovery.Molecules and cells · 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 assembly of type IIA topoisomerase DNA cleavage-religation center.Nucleic acids research · 2024Article
- The liquid-liquid phase separation signature predicts the prognosis and immunotherapy response in hepatocellular carcinoma.Journal of cellular and molecular medicine · 2024Article
- Gyrase and Topoisomerase IV: Recycling Old Targets for New Antibacterials to Combat Fluoroquinolone Resistance.ACS infectious diseases · 2024Review
- Deubiquitinase USP7 stabilizes KDM5B and promotes tumor progression and cisplatin resistance in nasopharyngeal carcinoma through the ZBTB16/TOP2A axis.Cell death and differentiation · 2024Article
- Telling Your Right Hand from Your Left: The Effects of DNA Supercoil Handedness on the Actions of Type II Topoisomerases.International journal of molecular sciences · 2023Review
- Exploration of anti-leukemic effect of soft coral-derived 13-acetoxysarcocrassolide: Induction of apoptosis via oxidative stress as a potent inhibitor of heat shock protein 90 and topoisomerase II.The Kaohsiung journal of medical sciences · 2023Article
- Extensive Bioinformatics Analyses Reveal a Phylogenetically Conserved Winged Helix (WH) Domain (Zτ) of Topoisomerase IIα, Elucidating Its Very High Affinity for Left-Handed Z-DNA and Suggesting Novel Putative Functions.International journal of molecular sciences · 2023Article
- Article
- Unveiling the interdomain dynamics of type II DNA topoisomerase through all-atom simulations: Implications for understanding its catalytic cycle.Computational and structural biotechnology journal · 2023Article
- Catalytic Mechanism of ATP Hydrolysis in the ATPase Domain of Human DNA Topoisomerase IIα.Journal of chemical information and modeling · 2022Article
- Recurrent mutations in topoisomerase IIα cause a previously undescribed mutator phenotype in human cancers.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Identification of Common Hub Genes in Human Dermal Fibroblasts Stimulated by Mechanical Stretch at Both the Early and Late Stages.Frontiers in surgery · 2022Article
- Review
- DNA topoisomerases: Advances in understanding of cellular roles and multi-protein complexes via structure-function analysis.BioEssays : news and reviews in molecular, cellular and developmental biology · 2021Review
- Identification of hub genes in triple-negative breast cancer by integrated bioinformatics analysis.Gland surgery · 2021Article
- A novel RNA sequencing-based risk score model to predict papillary thyroid carcinoma recurrence.Clinical & experimental metastasis · 2020Article
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Authors and funding
7 authors.
Funding
Abstract
Topoisomerase II resolves intrinsic topological problems of double-stranded DNA. As part of its essential cellular functions, the enzyme generates DNA breaks, but the regulation of this potentially dangerous process is not well understood. Here we report single-molecule fluorescence experiments that reveal a previously uncharacterized sequence of events during DNA cleavage by topoisomerase II: nonspecific DNA binding, sequence-specific DNA bending, and stochastic cleavage of DNA. We have identified unexpected structural roles of Mg(2+) ions coordinated in the TOPRIM (topoisomerase-primase) domain in inducing cleavage-competent DNA bending. A break at one scissile bond dramatically stabilized DNA bending, explaining how two scission events in opposing strands can be coordinated to achieve a high probability of double-stranded cleavage. Clamping of the protein N-gate greatly enhanced the rate and degree of DNA bending, resulting in a significant stimulation of the DNA cleavage and opening reactions. Our data strongly suggest that the accurate cleavage of DNA by topoisomerase II is regulated through a tight coordination with DNA bending.
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