THE GC-SELECTIVE LIGAND MITHRAMYCIN ALTERS THE STRUCTURE OF (AT)N SEQUENCES FLANKING ITS BINDING-SITES

DNA fragments containing (AT)n inserts cloned adjacent to putative mithramycin binding sites have been examined by footprinting experiments using a variety of nucleases in the presence of the drug. The results demonstrate that mithramycin induces a DNA structural change which renders adjacent (AT)n sequences sensitive to attack by DNase II. Significant changes are also revealed with DNase I and micrococcal nuclease. The results are consistent with a model in which mithramycin opens the DNA minor groove changing it to a structure which is locally more like A-DNA. © 1990.