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Nucleic Acids Research, 1988, Vol. 16, No. 23 11125-11139
© 1988

ENZYMOLOGY

Actinomycin D induced DNase I cleavage enhancement caused by sequence specific propagation of an altered DNA structure

Yao-qi Huang, Robert P. Rehfuss, Steven R. LaPlante1, Ellis Boudreau1, Philip N. Borer1 and Michael J. Lane

Division of Hematology/Oncology, Departments of Medicine and Microbiology, State University of New York - Health Science Center at Syracuse Syracuse, NY 13210, USA 1Department of Chemistry and NIH Resource for NMR and Data Processing, Syracuse University Syracuse, NY 13244, USA

Received August 29, 1988. Revised November 3, 1988. Accepted November 3, 1988.

Two DNA hexadecamers containing one central 5'-GC-3' base step have been examined by footprinting methodology in the presence and absence of actinomycin D. The results of these studies, coupled with imino proton NMR measurements indicate that the antitumor drug causes a change in DNA conformation at a distance from the actinomycin intercalation site in a molecule of sequence d[ATATATAGCTATATAT] that does not occur in d[AAAAAAAGCTTTTTTT] The experiments demonstrate that DNase I rate enhancements associated with actinomycin D binding are caused by ligand alteration of equilibrium DNA structure.


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