Newly replicated DNA is associated with DNA topoisomerase II in cultured rat prostatic adenocarcinoma cells

William G. Nelson, Leroy-Fong Liu, Donald S. Coffey

研究成果: 雜誌貢獻文章

152 引文 斯高帕斯(Scopus)

摘要

DNA topoisomerases have been proposed to function in a variety of genetic processes in both prokaryotes and eukaryotes1-3. Here, we have assessed the role of DNA topoisomerase II in mammalian DNA replication by determining the proximity of newly synthesized DNA to covalent enzyme-DNA complexes generated by treating cultured rat prostatic adenocarcinoma cells with teniposide. Teniposide (VM-26), an epipodophyllotoxin, is known to interact with mammalian DNA topoisomerase II so as to trap the enzyme in a covalent complex with DNA4-9. We have found that the teniposide-induced trapping of such complexes requires MgCl2, is stimulated by ATP and is inhibited by novobiocin. The formation of covalent complexes seems to be reversible on removal of teniposide. Furthermore, analysis of the covalent complexes formed between 3H-thymidine pulse-labelled DNA and topoisomerase II following teniposide treatment reveals a direct association of the enzyme with nascent DNA fragments. Our results suggest that DNA topoisomerase II may interact with newly replicated daughter DNA molecules near DNA replication forks in mammalian cells.

原文英語
頁(從 - 到)187-189
頁數3
期刊Nature
322
發行號6075
DOIs
出版狀態已發佈 - 1986
對外發佈Yes

ASJC Scopus subject areas

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