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Nucleic Acids Research, 1992, Vol. 20, No. 17 4553-4557
© 1992

MOLECULAR BIOLOGY

Gilvocarcin V exhibits both equilibrium DNA binding and UV light induced DNA adduct formation which is sequence context dependent

Robert M. Knobler*, F.Bernhard Radlwimmer1 and Michael J. Lane1,*

Second Department of Dermatology, University of Vienna Vienna, Austria 1 Department of Medicine, State University of New York—Health Science Center at Syracuse Syracuse, NY 13210, USA

* To whom correspondence should be addressed

Received May 27, 1992. Revised July 31, 1992. Accepted July 31, 1992.

The relative degree of both equilibrium binding and of ultraviolet light induced adduct formation for the antitumor antibiotic gilvocarcin V with two hexaecamer DNA sequence isomers, d[ATATATAGCTATATAT]2 and d[AAAAAAAGCTTTTTTT]2, was assessed. The experiments reveal that gilvocarcin V binds, under equilibrium conditions, and reacts, in the presence of exogenously applied UV light, more efficiently with the alternating purine:pyrimidine sequence hexadecamer than the homopurine:homopyrimidine duplex at identical gilvocarcin V to DNA duplex ratios. DNAse I digests of adduct containing duplexes derived from the d[AAAAAAAGCTTTTTTT]2 duplex, identified and isolated using gel shift assays employing denaturing polyacrylamide gels, confirm that gilvocarcin V adducts can be formed with thymine residues but suggest that adduct formation with either adenine or guanine residues is also possible.


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[Abstract] [Full Text]


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