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

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. 0167-4781/98/$ - see front matter (C) 1998 Elsevier Science B.V. All rights reserved.