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Nucleic Acids Research, 1994, Vol. 22, No. 19 3834-3839
© 1994

MOLECULAR BIOLOGY

Base sequence-independent distortions induced by interstrand cross-links in cis-diamminedichloroplatinum (ll)-modified DNA

Jean-Marc Malinge, Cécile Pérez and Marc Leng*

Centre de Biophysique Moléculaire, CNRS, 1A Avenue de la Recherche Scientifique, 45071 Orléans cédex 02, France

* To whom correspondence should be addressed

Received July 23, 1994. Revised August 18, 1994. Accepted August 18, 1994.

Physico-chemical and immunological studies have been done in order to further characterize the distorsions induced in DNA by the interstrand crosslinks formed between the antitumor drug cis-diamminedichloroplatinum (II) (cis-DDP) and two guanines on the opposite strands of DNA at the d(GC/GC) sites. Bending (45°) and unwinding (79 ± 4°) were determined from the electrophoretic mobility of multimers of 21- 24-base pairs double-stranded oligonucleotides containing an interstrand cross-link in the central sequence d(TGCT/AGCA). The distorsions induced by the interstrand cross-link in the three 22-base pairs oligonucleotides d(TGCT/AGCA), d(AGCT/AGCT) and d(CGCT/AGCG) were compared by means of gel electrophoresis, circular dichroism, phenanthroline-copper footprinting and antibodies specifically directed against cis-DDP interstrand crosslinks. The four different technical approaches indicate that the distorsions are independent of the chemical nature of the base pairs adjacent to the interstrand cross-link. The general conclusion is that the interstrand cross-link induces a bending and in particular an unwinding larger than other platinum adducts and the distorsions are independent of the nature of the bases (purine or pyrimidine) adjacent to the d(GC/GC) site.


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