Etoposide, a chemotherapeutic poison of type IIA eukaryotic topoisomerases (topo IIs), promotes topo II to compact DNA by trapping DNA loops, creates DNA double-strand breaks, causes topo II to resist relocation, and pauses the ability of topoisomerases to relax DNA supercoiling. Through these mechanisms, etoposide converts topo II into a roadblock to DNA processing.
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This is a summary of: Le, T. T. et al. Etoposide promotes DNA loop trapping and barrier formation by topoisomerase II. Nat. Chem. Biol. https://doi.org/10.1038/s41589-022-01235-9 (2023).
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Topoisomerase II and etoposide — a tangled tale. Nat Chem Biol (2023). https://doi.org/10.1038/s41589-022-01236-8