Selective inhibition of ribosomal RNA synthesis in HeLa cells by nogalamycin, a dA:dT binding antibiotic

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Nogalamycin is known to bind to DNA and inhibit its use as a template for RNA synthesis. Since the antibiotic has been reported to bind to the dA:dT pair of the DNA double helix, it was explored as a possible selective inhibitor of the synthesis of DNA-like RNA. A concentration of 1.39·10 −7 M was found to produce close to 50% inhibition of cytidine incorporation into the nucleic acids of HeLa cells; 30 times this concentration had no significant immediate effect on protein synthesis. The concentration of 1.39·10 −7 M nogalamycin produced some inhibition of the synthesis of all nucleic acids in increasing order of magnitude DNA < DNA-likeRNA < tRNA, 5-S RNA < rRNA. The selectivity for rRNA was pronounced but a little less than that of actinomycin D. No evidence of a marked increase in the rate of degradation of any nucleic acid was found, nor did it prevent the maturation of the small amount of ribosomal precursor RNA formed in its presence. Various hypotheses concerning the unique sensitivity of rRNA synthesis to these drugs were evaluated.