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
收藏
页码:83 / 106
页数:24
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