Inhibition of the RNA polymerase-catalyzed synthesis of RNA by marcellomycin. Preferential interference of the inhibitor with the stabilization of the ternary promoter-RNA polymerase-nascent RNA complex.
Marcellomycin is a strong inhibitor of the Escherichia coli RNA polymerase-catalyzed synthesis of RNA from the strong A promoters of bacteriophage T7 DNA. Marcellomycin inhibits preferentially the last phase of transcription initiation. During this phase a stabilized ternary complex is formed consisting of RNA polymerase, DNA template, and a nascent RNA oligonucleotide about 11 nucleotides long, resulting from the extension of the RNA dinucleotide component of the corresponding early ternary complex. Marcellomycin is also responsible for minor inhibition of the formation of the open binary RNA polymerase-template complex, which serves as the precursor of the ternary complex. These findings suggest that marcellomycin may be a potentially useful tool in the study of the late stages of transcription initiation. The present findings may also contribute to a better overall understanding of the mode of drug action at the level of individual genes.
Kriebardis
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Department of Biochemistry and Biophysics, Stritch School of Medicine, Loyola University, Maywood, Illinois 60153.
Aktipis
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D018943:Anthracyclines; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors*; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D007700:Kinetics; D009279:Naphthacenes / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D013604:T-Phages / Q000235:genetics / Q000378:metabolism; D013698:Templates, Genetic; D014158:Transcription, Genetic / Q000187:drug effects*
D018943:Anthracyclines; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D009279:Naphthacenes; C015338:marcellomycin; D012321:DNA-Directed RNA Polymerases