Rowe T C, Couto E, Kroll D J
NCI Monogr. 1987(4):49-53.
Camptothecin is a cytotoxic drug which inhibits cellular nucleic acid synthesis. Associated with this inhibition is the induction of protein-linked DNA strand breaks. Recent studies have demonstrated that camptothecin interferes with the DNA breakage and rejoining activity of the enzyme DNA topoisomerase I and stabilizes a cleavable complex between this enzyme and DNA. Treatment of this complex with a protein denaturant results in DNA strand breaks and the covalent attachment of topoisomerase to the 3'-end of the DNA breaks. In this paper we have mapped the camptothecin-induced DNA breaks on the hsp 70 heat-shock gene in cultured Drosophila cells. Drug-induced breaks are present primarily within the coding region of this gene and occur only when transcription of this gene is activated by heat. Camptothecin (20 microM) was also observed to inhibit heat-induced hsp 70 transcription greater than 70%. The possible role of topoisomerase I in hsp 70 heat-shock gene transcription is discussed.
喜树碱是一种细胞毒性药物，可抑制细胞核酸合成。这种抑制作用伴随着蛋白质连接的DNA链断裂的诱导。最近的研究表明，喜树碱会干扰DNA拓扑异构酶I的DNA断裂和重新连接活性，并稳定该酶与DNA之间的可裂解复合物。用蛋白质变性剂处理这种复合物会导致DNA链断裂以及拓扑异构酶与DNA断裂的3'末端共价结合。在本文中，我们绘制了喜树碱诱导的培养果蝇细胞中hsp 70热休克基因上的DNA断裂图谱。药物诱导的断裂主要出现在该基因的编码区内，并且仅在该基因的转录因热激活时才会发生。还观察到喜树碱（20 microM）抑制热诱导的hsp 70转录超过70%。本文讨论了拓扑异构酶I在hsp 70热休克基因转录中的可能作用。
