Recent advances in understanding how actinomycin binds to DNA have suggested its mechanism of action. Actinomycin binds to a premelted DNA conformation present within the transcriptional complex. This immobilizes the complex, interfering with the elongation of growing RNA chains. The model has a number of implications for understanding RNA synthesis.Understanding the mechanism ofaction ofactinomycin D has long been a major goal in cancer research and in molecular biology. Actinomycin is a cyclic polypeptide-containing antibiotic that binds to DNA and inhibits RNA synthesis (1)(2)(3)(4) Here, I propose a modification to our actinomycin-DNA binding model that allows one to understand its mechanism of action. I propose that actinomycin binds to a premelted DNA conformation-called /3-DNA-found within the transcriptional complex. This acts to immobilize (or pin) the complex, preventing the elongation of growing RNA chains. The model has implications for understanding the early melting behavior of DNA and, along with this, suggests a mechanism to understand the formation of the RNA polymerase-promoter tight binding complex. Other possible implications are discussed.Actinomycin-DNA Binding Model. Fig. la summarizes key structural features of my model to understand how actinomycin binds to DNA.As in our earlier model, the phenoxazone ring system on actinomycin intercalates between (base paired) dinucleotide sequences of the type d(pGpX) (where X = C, T, A, or G), while pentapeptide chains lie in the narrow groove of the structure, hydrogen bonding [in the case of d(pGpC) sequences] to guanine residues on opposite chains. Although

No abstract

No abstract

No abstract

No abstract