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

被引：533

作者：

Pommier, Y ^{[1
]}

Pourquier, P ^{[1
]}

Fan, Y ^{[1
]}

Strumberg, D ^{[1
]}

机构：

[1] NCI, Mol Pharmacol Lab, Div Basic Sci, Bethesda, MD 20892 USA

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION | 1998年 / 1400卷 / 1-3期

关键词：

camptothecin; DNA repair; DNA replication; recombination; gene regulation; DNA break;

D O I：

10.1016/S0167-4781(98)00129-8

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：83 / 106

页数：24

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