The inhibition of RNA and DNA polymerases by hedamycin

Abstract

1. The interaction of hedamycin, an antibiotic from Streptomyces griseoruber with polynucleotides and the effect of this interaction on their template capacity in nucleic acid synthesis have been studied. A peak at 430 mμ in the spectrum of hedamycin is depressed and shifted to higher wave lengths in the presence of calf thymus DNA. The maximum change occurs with a hedamycin to DNA-P ratio of 1:5 and is decreased by half at high ionic strength. The presence of hedamycin increases the thermal transition temperature of calf thymus DNA and the strictly alternating deoxyadenylate-deoxythymidylate copolymer (d(A-T n) decreases the buoyant density of d(A-T) n and increases the viscosity of calf thymus DNA. 2. Hedamycin is a potent inhibitor of calf thymus DNA- and d(A-T) n-directed synthesis of RNA by Escherichia coli RNA polymerase. DNA synthesis by E. coli DNA polymerase with the same templates is also inhibited by hedamycin, but requires 3–5-fold greater concentrations of antibiotic for comparable inhibition. The degree of inhibition of RNA synthesis by the antibiotic is only slightly dependent on the DNA concentration and is independent of RNA polymerase concentration. Hedamycin is able to block RNA polymerization even after its initiation. A comparison of the effect of hedamycin on RNA synthesis using a variety of polynucleotides as templates suggests there is no strict base specificity in the interaction of hedamycin and polynucleotides. The inhibition of RNA synthesis by hedamycin, however, is greater when the template is double-stranded rather than single-stranded.