Actinomycin D facilitates transition of AT domains in molecules of sequence (AT)nAGCT(AT)n to a DNAse I detectable alternating structure

• Published in: Nucleic acids research Vol. 15; no. 2; pp. 839 - 852
• Main Authors: LANE, M. J, LAPLANTE, S, REHFUSS, R. P, BORER, P. N, CANTOR, C. R
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 26-01-1987
• Subjects: Adenine; Applied sciences; Base Composition; Base Sequence; Dactinomycin - pharmacology; Deoxyribonuclease I - metabolism; Exact sciences and technology; Kinetics; Magnetic Resonance Spectroscopy; Oligodeoxyribonucleotides - chemical synthesis; Other techniques and industries; Substrate Specificity; Thymine
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/15.2.839

The interaction of actinomycin D with (AT)nAGCT(AT)n (where n = 2, 3, or 4) was investigated using a combination of imino proton NMR and DNAse I digestion. The stoichiometry of the interaction appears to be one:one with the actinomycin chromophore intercalated between the two GC base pairs. This binding event facilitates the conversion of the flanking repetitive AT regions to an alternating conformation characterized by induced sensitivity of the ApT sequences to attack by DNAse I. The neighboring TpA sequences do not exhibit rate changes as a function of binding of the drug. The potential relevance of such ligand induced DNA structural alterations is discussed.