Pourquier P, Pommier Y
Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Adv Cancer Res. 2001;80:189-216. doi: 10.1016/s0065-230x(01)80016-6.
Topoisomerase I is a ubiquitous and essential enzyme in multicellular organisms. It is involved in multiple DNA transactions including DNA replication, transcription, chromosome condensation and decondensation, and probably DNA recombination. Besides its activity of DNA relaxation necessary to eliminate torsional stresses associated with these processes, topoisomerase I may have other functions related to its interaction with other cellular proteins. Topoisomerase I is the target of the novel anticancer drugs, the camptothecins. Recently a broad range of physiological and environmentally-induced DNA modifications have also been shown to poison topoisomerases. This review summarizes the various factors that enhance or suppress top1 cleavage complexes and discusses the significance of such effects. We also review the different mechanisms that have been proposed for the repair of topoisomerase I-mediated DNA lesions.
拓扑异构酶I是多细胞生物中一种普遍存在且必不可少的酶。它参与多种DNA事务，包括DNA复制、转录、染色体凝聚和解凝聚，以及可能的DNA重组。除了其消除与这些过程相关的扭转应力所必需的DNA松弛活性外，拓扑异构酶I可能还有其他与其与其他细胞蛋白相互作用相关的功能。拓扑异构酶I是新型抗癌药物喜树碱类的作用靶点。最近还发现，多种生理和环境诱导的DNA修饰也会使拓扑异构酶中毒。本文综述了增强或抑制top1切割复合物的各种因素，并讨论了这些作用的意义。我们还综述了针对拓扑异构酶I介导的DNA损伤修复提出的不同机制。
