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Mechanism of action of eukaryotic DNA topoisomerase I and drugs targeted to the enzyme

Abstract : DNA topoisomerase I is essential for cellular metabolism and survival. It is also the target of a novel class of anticancer drugs active against previously refractory solid tumors, the camptothecins. The present review describes the topoisomerase I catalytic mechanisms with particular emphasis on the cleavage complex that represents the enzyme's catalytic intermediate and the site of action for camptothecins. Roles of topoisomerase I in DNA replication, transcription and recombination are also reviewed. Because of the importance of topoisomerase I as a chemotherapeutic target, we review the mechanisms of action of camptothecins and the other topoisomerase I inhibitors identified to date.
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https://www.hal.inserm.fr/inserm-02438240
Contributor : Philippe Pourquier <>
Submitted on : Tuesday, January 14, 2020 - 10:35:13 AM
Last modification on : Tuesday, July 7, 2020 - 3:05:52 PM

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Yves Pommier, Philippe Pourquier, Yi Fan, Dirk Strumberg. Mechanism of action of eukaryotic DNA topoisomerase I and drugs targeted to the enzyme. BBA - Gene Structure and Expression, Elsevier, 1998, 1400 (1-3), pp.83-106. ⟨10.1016/s0167-4781(98)00129-8⟩. ⟨inserm-02438240⟩

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