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Nucleic Acids Research, 1994, Vol. 22, No. 24 5241-5246
© 1994

Articles

Daunomycin modifies the sequence-selective recognition of DNA by actinomycin

Gareth S. Ridge, Christian Bailly+, David E. Graves1 and Michael J. Waring*,

Department of Pharmacology, University of Cambridge, Tennis Court Road Cambridge CB2 1QJ, UK 1Department of Chemistry, University of Mississippi MS 38677, USA

*To whom correspondence should be addressed

+Premanent address: lnsthut de Recherche sur Ic Cancer, INSERM Unite 124, Place de Verdun, 59045 Lille, France

Received September 16, 1994. Accepted October 31, 1994.

The antltumour antibiotic actinomycin D normally binds to DNA by intercalation at sequences containing the CpG step, but In the presence of daunomycin It has been reported to Interact with poly(dA-dT). This observation has neither been confirmed nor explained. Here we have used a photoreactlve 7-azido derivative of actinomycin to study the effect of daunomycin on its binding to three DNA fragments. Daunomycin did indeed alter the binding of actinomycin to the DNA, such that the antibiotic was displaced from Its primary GpC sites onto secondary sites in the DNA, though not to AT regions especially. These findings suggest a possible scientific explanation for the Increased toxldty seen during combination chemotherapy with these two drugs.


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