The Role of Deoxyribonucleic Acid in Ribonucleic Acid Synthesis, Iii. The Inhibition of the Enzymatic Synthesis of Ribonucleic Acid and Deoxyribonucleic Acid by Actinomycin D and Proflavin

Abstract

Actinomycin D is one of a number of polypeptide antibiotics isolated in Waksman's laboratory.1' 2 Bacteriostatic effects, particularly on gram positive bacteria, and antitumor activity have been attributed to this compound.2 3 Kirk4 has demonstrated that the addition of actinomycin D (0.2 to 0.5 ,4M) to exponentially growing cultures of Staphylococcus aureus stops RNA synthesis immediately. This effect is rapidly followed by an inhibition of protein synthesis, and later by a partial inhibition of DNA synthesis. The action of this compound is not related directly to energy production since both respiration and glycolysis of inhibited cells are unaffected by concentrations up to 0.1 mM.4 Kirk also demonstrated that the combination of DNA and actinomycin D results in a spectral change of the latter compound. These observations suggest the formation of a complex between these two compounds since Kawamata and Imanishi5 found no interaction of actinomycin and RNA and the reaction appears to be relatively specific for DNA. Although Rauen et al.6 have reported complex formation between actinomycin and RNA, 100 times more RNA than DNA is required.Two recent reports have suggested that actinomycin acts by inhibiting the synthesis of "messenger" RNA. Nakata et al.7 have shown that reproduction of T2

Dna Dependence of Plastid Differentiation Inhibition by Actinomycin D

“…For this purpose, we have used actinomycin D, a highly specific inhibitor of R N A -D N A polymerase activity (6). Actinomycin effect is exerted on the template by complexing specifically and firmly with the primer DNA.…”

Plasmid-instability in acrA Mutants of Escherichia coli K12

“…In vitro experiments have shown that acridines are intercalated between specific adjacent base pairs in DNA (Lerman, 1963) and inhibit synthesis of DNA (Hurwitz, Furth, Malamy &Alexander, 1962). The base specificity of the affinity has been demonstrated to differ according to the kinds of acridines (Tubbs, Eitmars & van Winkle, 1964;Weisblum & de Haseth, 1972).…”

THE BASE COMPOSITION OF RIBONUCLEIC ACID IN LAMPBRUSH CHROMOSOMES, NUCLEOLI, NUCLEAR SAP, AND CYTOPLASM OF TRITURUS OOCYTES

“…RNA x synthesis in isolated thymus nuclei was found to be DNA dependent (Allfrey and Mirsky, 1962) and a similar dependence may apply to all cellular RNA synthesis (Hurwitz et al, 1962; also for references). The restriction of DNA to the chromosomes gives chRNA a unique position since it should contain RNA newly synthesized under the influence of DNA.…”