拓扑异构酶
酶
抄写(语言学)
医学
DNA
聚合酶
生物化学
药理学
生物
癌症研究
语言学
哲学
作者
Sylvie Guichard,Mary K. Danks
出处
期刊:Current Opinion in Oncology
[Ovid Technologies (Wolters Kluwer)]
日期:1999-11-01
卷期号:11 (6): 482-482
被引量:16
标识
DOI:10.1097/00001622-199911000-00009
摘要
DNA topoisomerases catalyze changes in the topology of DNA. Recently, other functions have also been reported for these enzymes. For example, topoisomerase I participates in transcription by RNA polymerases I, II, and III, and also has a kinase activity. Topoisomerase I binds directly to at least two helicases, nucleolin and SV40 T antigen, and mechanistic studies show that T antigen alters the function of topoisomerase I. Additional protein and nucleotide interactions for both topoisomerases I and II suggest that each protein is multifunctional. It may be that the multifunctional nature of these enzymes is the basis for the antitumor activity seen with inhibitors of these enzymes. Clinical trials with combinations of CPT-11 and 5-fluorouracil for the treatment of colon cancer, and preclinical studies with CPT-11 and vincristine are particularly encouraging. Protracted schedules of administration of topoisomerase inhibitors will likely have greater antitumor effect than more concentrated, higher dose exposures, but a systematic determination of optimal schedules of administration is needed.
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