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.
This is a preview of subscription content, log in via an institution to check access.
References
Baldwin, E. L. & Osheroff, N. Etoposide, topoisomerase II and cancer. Curr. Med. Chem. Anticancer Agents 5, 363–372 (2005). A review article on etoposide as a broadly used chemotherapeutic topo II poison.
Wu, C. C. et al. Structural basis of type II topoisomerase inhibition by the anticancer drug etoposide. Science 333, 459–462 (2011). This paper reports the crystal structure of a DNA cleavage complex bound with etoposide.
Brower-Toland, B. D. et al. Mechanical disruption of individual nucleosomes reveals a reversible multistage release of DNA. Proc. Natl Acad. Sci. USA 99, 1960–1965 (2002). This paper describes the DNA stretching methods to characterize interaction strengths and DNA release from bound proteins.
Le, T. T. et al. Mfd dynamically regulates transcription via a release and catch-up Mechanism. Cell 172, 344–357.e15 (2018). This paper describes the DNA unzipping mapper to characterize the strengths and locations of protein–DNA interactions.
Strick, T. R., Croquette, V. & Bensimon, D. Single-molecule analysis of DNA uncoiling by a type II topoisomerase. Nature 404, 901–904 (2000). This paper describes the use of magnetic tweezers for detecting topo II relaxation of DNA supercoiling.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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).
Rights and permissions
About this article
Cite this article
Topoisomerase II and etoposide — a tangled tale. Nat Chem Biol 19, 546–547 (2023). https://doi.org/10.1038/s41589-022-01236-8
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41589-022-01236-8
- Springer Nature America, Inc.