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Nucleic Acids Research, 1985, Vol. 13, No. 24 8695-8714
© 1985

Articles

Investigations into the sequence-selective binding of mithramycin and related ligands to DNA

Keith R. Fox and Nigel R. Howarth

Department of Pharmacology, University of Cambridge, Medical School Hills Road, Cambridge CB2 2QD, UK

Received October 29, 1985. Revised November 25, 1985. Accepted November 25, 1985.

The preferred binding sites for mithramycin on four different DNA fragments have been investigated by DNAase I footprinting. Sites containing at least two contiguous GC base pairs are protected by the antibiotic, the preferred binding site consisting of the dinucleotide step GpG (or CpC). Related antibiotics chromomycin and olivomycin produce similar, but not identical footprinting patterns suggesting that they can recognize other sequences as well. All three antibiotics induce enhanced rates of enzyme cleavage at regions flanking some of their binding sites. These effects are generally observed in runs of A and T and are attributed to DNA structural variations induced in the vicinity of the ligand binding site. The reaction of dimethylsulphate with N7 of guanine was modified by the presence of mithramycin so that we cannot exclude the possibility that these antibiotics bind to DNA via the major groove.


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