title: Novobiocin inhibits RNA polymerase III transcription in vitro by a mechanism distinct from DNA topoisomerase II.
abstract: The role of DNA topoisomerases in eucaryotic class III gene transcription in vitro has been studied through the use of inhibitory drugs and antisera to DNA topoisomerases I and II. The DNA topoisomerase II inhibitors, novobiocin and coumermycin AI, were found to inhibit transcription of cloned 5S and tRNA genes. Novobiocin acts by interfering with an ATP-requiring step in the pathway to stable preinitiation complex formation. However, it is unlikely that this step reflects the enzymatic action of DNA topoisomerase II since a specific inhibitor of this enzyme (VM-26) and anti-DNA topoisomerase II antibodies fail to inhibit transcription under conditions where topoisomerase II enzymatic activity is inhibited. Similarly, a specific inhibitor of DNA topoisomerase I (camptothecin) and anti-DNA topoisomerase I antibodies fail to inhibit class III gene transcription. These results argue against a role for either DNA topoisomerase in 5S or tRNA gene transcription in vitro.
mesh_terms: D049933:Aminocoumarins; D002166:Camptothecin / Q000494:pharmacology; D003374:Coumarins / Q000494:pharmacology; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors*; D006367:HeLa Cells; D009675:Novobiocin / Q000494:pharmacology*; D012320:RNA Polymerase III / Q000037:antagonists & inhibitors*; D012335:RNA, Ribosomal / Q000096:biosynthesis; D012343:RNA, Transfer / Q000096:biosynthesis; D013713:Teniposide / Q000494:pharmacology; D059005:Topoisomerase II Inhibitors; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D049933:Aminocoumarins; D003374:Coumarins; D012335:RNA, Ribosomal; D059005:Topoisomerase II Inhibitors; D009675:Novobiocin; D012343:RNA, Transfer; D013713:Teniposide; D012321:DNA-Directed RNA Polymerases; D012320:RNA Polymerase III; C004628:coumermycin; D002166:Camptothecin