BASE SEQUENCE-INDEPENDENT DISTORSIONS INDUCED BY INTERSTRAND CROSS-LINKS IN CIS-DIAMINEDICHLOROPLATINUM (II)-MODIFIED DNA

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 diamminedichloroplatinum (II) (cis-DDP) guanines on the opposite strands of DNA at the d(GC/GC) sites. Bending (45 degrees) and unwinding(79 +/- 4 degrees) 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 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.