Mechanism of action of eukaryotic DNA topoisomerase I and drugs targeted to the enzyme - PubMed (original) (raw)

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

Y Pommier et al. Biochim Biophys Acta. 1998.

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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