Selective nucleosome disruption by drugs that bind in the minor groove of DNA.

摘要: Previous studies have shown that drugs which bind in the DNA minor groove reduce curvature of bent DNA. In this article, we examined effects these on nucleosome assembly molecules display different degrees intrinsic curvature. DAPI (4,6-diamidino-2-phenylindole) inhibited a histone octamer onto 192-base pair circular fragment from Caenorhabditis elegans and destabilized was previously assembled segment. The inhibitory effect highly selective since it not seen with nonbent molecules, noncircular shapes, or total genomic This marked template specificity attributed to binding ligand multiple oligo A-tracts distributed over length fragment. A likely mechanism for is bound prevents further compression into required nucleosomes. To characterize drug chromatin formation, 322-base contained element flanking segment position along then determined using variety nuclease probes including exonuclease III, micrococcal nuclease, DNase I, restriction enzymes. results revealed preferentially positioned absence but sequence presence drug. also induced directional movement when preassembled exposed under physiologically relevant conditions.