ArticlePloS one2013
Replication-dependent and transcription-dependent mechanisms of DNA double-strand break induction by the topoisomerase 2-targeting drug etoposide.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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43 citing papers in PubMed, 76 citations in OpenAlex.
- A multispecies toolkit ofProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Transcription-coupled nucleotide excision repair protects against genomic instability and cell death induced by the liver toxin methyleugenol.Cell death & disease · 2026Article
- LFC-Lab on a chip · 2026Article
- A simple method to efficiently generate structural variation in plants.PLoS genetics · 2025Article
- FN9-10ELP, an ECM-Mimetic Fusion Protein, Protects Human Mesenchymal Stem Cells from Etoposide-Induced Senescence.International journal of molecular sciences · 2025Article
- Functional variants of CFAP410 affect the DNA damage response leading to motor neuron degeneration - Implications for ALS.iScience · 2025Article
- Structural Mechanisms of Topoisomerase-Targeting Drugs.Annual review of biochemistry · 2025Review
- Reduction of DNA Topoisomerase Top2 Reprograms the Epigenetic Landscape and Extends Health and Life Span Across Species.Aging cell · 2025Article
- Analyzing Topoisomerase II Cleavage Complexes Using Flow Cytometry.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Use of Xenopus Egg Extracts to Study the Effects of Topoisomerase Poisons During Vertebrate DNA Replication.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Optimization of concentrations and exposure durations of commonly used positive controls in the in vitro alkaline comet assay.Toxicology research · 2024Article
- Genome Instability Induced by Topoisomerase Misfunction.International journal of molecular sciences · 2024Review
- Mitochondrial DNA is a sensitive surrogate and oxidative stress target in oral cancer cells.PloS one · 2024Article
- Etoposide promotes DNA loop trapping and barrier formation by topoisomerase II.Nature chemical biology · 2023Article
- Short-Term Starvation Weakens the Efficacy of Cell Cycle Specific Chemotherapy Drugs through G1 Arrest.International journal of molecular sciences · 2023Article
- The functions and roles of C2H2 zinc finger proteins in hepatocellular carcinoma.Frontiers in physiology · 2023Review
- GADD34 activates p53 and may have utility as a marker of atherosclerosis.Frontiers in medicine · 2023Article
- Article
- Topoisomerase II poisons inhibit vertebrate DNA replication through distinct mechanisms.The EMBO journal · 2022Article
- Expanding the Study of the Cytotoxicity of Incomptines A and B against Leukemia Cells.Molecules (Basel, Switzerland) · 2022Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Etoposide is a DNA topoisomerase 2-targeting drug widely used for the treatment of cancer. The cytoxicity of etoposide correlates with the generation of DNA double-strand breaks (DSBs), but the mechanism of how it induces DSBs in cells is still poorly understood. Catalytically, etoposide inhibits the re-ligation reaction of Top2 after it nicks the two strands of DNA, trapping it in a cleavable complex consisting of two Top2 subunits covalently linked to the 5' ends of DNA (Top2cc). Top2cc is not directly recognized as a true DSB by cells because the two subunits interact strongly with each other to hold the two ends of DNA together. In this study we have investigated the cellular mechanisms that convert Top2ccs into true DSBs. Our data suggest that there are two mechanisms, one dependent on active replication and the other dependent on proteolysis and transcription. The relative contribution of each mechanism is affected by the concentration of etoposide. We also find that Top2α is the major isoform mediating the replication-dependent mechanism and both Top2α and Top2 mediate the transcription-dependent mechanism. These findings are potentially of great significance to the improvement of etoposide's efficacy in cancer therapy.
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