Nucleic Acids Research, 1987, Vol. 15, No. 20 8547-8559
© 1987
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Novoblocin inhibits initiation of RNA potymerase Il-directed transcription of the moose metaDothiondn-I gene independent of its effect oo DNA topoisomerase II
Department of Pharmacology and Tbe Cell and Molecular Biology Center, Pennsylvania State University, College of Medicine Hershey, PA 17033, USA
*To whom correspondence should be addressed
Received June 17, 1987. Revised September 17, 1987. Accepted September 17, 1987.
The requirement for ATP hydrolysis in the initiation of RNA polymerase II (Pol II)-directed transcription and the relationship between ATP and novobiocin action led us to Investigate whether novoblocin could inhibit transcription of the House netallothioneln-I (MT-I) gene. Novobiocin Inhibited the MT-I gene transcription in a fractionated rat hepatoma nuclear extract In a dose-dependent manner by direct interaction with a nuclear factor(s). This interaction prevented formation of stable prelnitlation complexes but did not affect elongation of MT-I mRNA. Preincubatlon of the nuclear extract with ATP prevented the action of novobiocin on MT-I gene transcription. Although novobiocin is known to Inhibit DNA topolsomerase II, VM-26, a specific inhibitor of this enzyme had no effect on the transcription. These results indicate that novobiocin blocks the Pol Il-directed transcription by Inhibiting formation of preinitiation complexes at an ATP-dependent step.
+Present address: The Wistar Institute, Spruce St., Philadelphia, PA, USA
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