Base sequence-independent distorsions induced by interstrand cross-links in cis-diamminedichloroplatinum (II)-modified DNA.
Physico-chemical and immunological studies have been done in order to further characterize the distorsions induced in DNA by the interstrand cross-links 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 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 cross-links. 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.
Malinge
J M
JM
Centre de Biophysique Moléculaire, CNRS, Orléans, France.
Pérez
C
C
Leng
M
M
D001483:Base Sequence; D002942:Circular Dichroism; D002945:Cisplatin / Q000494:pharmacology*; D003300:Copper; D003432:Cross-Linking Reagents; D004247:DNA / Q000737:chemistry* / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation / Q000187:drug effects*; D010618:Phenanthrolines
D003432:Cross-Linking Reagents; D010618:Phenanthrolines; D003300:Copper; D004247:DNA; D002945:Cisplatin