Effect of Distamycin A on T4‐DNA‐Directed RNA Synthesis

Distamycin inhibits the transcription of T4‐DNA by Escherichia coli RNA polymerase. The inhibition of RNA synthesis is predominantly due to a decrease in RNA chain initiation. The average chain length of the RNA which is synthesized in the presence of the antibiotic remains unaltered up to a ratio of 1 mole distamycin per 30 nucleotides of the DNA. The impairment of the initiation of RNA synthesis is explained by an inhibition of the binding of the RNA polymerase to the DNA. The binding of the RNA polymerase holoenzyme to DNA is affected to a much greater extent than the binding of the core enzyme. A preincubation of RNA polymerase holoenzyme and DNA at 30°C renders the RNA synthesis resistant to the drug. Preincubation of core enzyme and DNA is without any effect. Based on these results it is concluded that distamycin predominantly affects the binding of RNA polymerase to the specific binding sites.