Van Dyke M W, Roeder R G
Nucleic Acids Res. 1987 Jun 11;15(11):4365-74. doi: 10.1093/nar/15.11.4365.
Novobiocin has been shown to inhibit class III gene transcription from both chromatin and non-chromatin templates. Since novobiocin is a well characterized inhibitor of type II DNA topoisomerases, it has been postulated that a gyrase activity is necessary for transcription. Using DNase I footprinting, we show here that novobiocin inhibits the specific binding of polymerase III transcription factors TFIIIA and TFIIIC to the promoters of the 5S RNA and VA RNA genes, respectively. Concentrations of novobiocin employed were comparable to those necessary to inhibit HeLa topoisomerase II. In vitro transcription assays, performed under equivalent conditions, demonstrated that similar novobiocin concentrations were necessary for transcription inhibition. These results strongly suggest that novobiocin interferes with transcription by inhibiting specific protein-DNA interactions.
新生霉素已被证明可抑制来自染色质和非染色质模板的III类基因转录。由于新生霉素是一种已被充分表征的II型DNA拓扑异构酶抑制剂，因此有人推测，一种促旋酶活性对于转录是必需的。使用DNA酶I足迹法，我们在此表明，新生霉素分别抑制聚合酶III转录因子TFIIIA和TFIIIC与5S RNA和VA RNA基因启动子的特异性结合。所用新生霉素的浓度与抑制HeLa拓扑异构酶II所需的浓度相当。在等效条件下进行的体外转录试验表明，类似的新生霉素浓度对于转录抑制是必需的。这些结果有力地表明，新生霉素通过抑制特定的蛋白质-DNA相互作用来干扰转录。
