Nucleotide sequence specificity of DNA cleavage by iron-bleomycin. Alteration on ethidium bromide-, actinomycin-, and distamycin-intercalated DNA

The specific nucleotide recognition and sequence-specific cleavage of DNA by bleomycin (BLM) antibiotics are a typical example of macromolecular receptor-drug interaction in the field of chemotherapy. The present results demonstrate that ethidium bromide, distamycin A, and actinomycin D evidently altered the nucleotide sequence-specific mode of DNA breakage by the iron-BLM system, which cleaves isolated DNA preferentially at G-C (5' leads to 3') and G-T (5' leads to 3') sequences. In the presence of ethidium bromide, the most preferred cleavage site was the sequence G-T at position 52 to 53. Of special interest is marked alteration of the nucleotide sequence-specific mode by distamycin A. This intercalator masked the cleavages at G-T and G-A sequences, and produced higher specificity for G-C sequences than that of iron-BLM only. In the case of actinomycin D, the preferred sequence groups of DNA breakage were shifted from G-C sequences to G-A (43 to 44) and G-T (52 to 53) sequences. Certain intercalating agents are very available for the investigations of site-specific recognition and cleavage of DNA by DNA-cleaving drugs such as BLM.