[Cluster melting of DNA-actinomycin complexes]

Sensitive methods of differential UV spectrophotometry and differential scanning microcalorimetry were used to study the interaction of small and large quantities of the natural antitumor antibiotic actinomycin D with clusters of native and fragmented calf thymus DNA during thermal melting. At micromolar (physiological) concentrations, actinomycin is incorporated in untwisted sites of DNA rather than in the double helix. Actinomycin stabilizes these sites and therefore slightly increases the overall melting temperature of DNA. The antibiotic effectively interacts with the nucleotides of native DNA at a ratio of 1 : 868, especially strongly with the clusters of satellite fractions and DNA fragments. At low concentrations, it stabilizes the "loose" clusters, i.e., those matching untwisted areas that melt first. At high concentrations, it destabilizes the double helix and causes the aggregation of DNA.