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PMID: 7937101 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Base sequence-independent distorsions induced by interstrand cross-links in cis-diamminedichloroplatinum (II)-modified DNA.

Nucleic acids research ·Vol. 22 ·No. 19 ·1994-09-25 ·Pages 3834-9

Malinge JM, Pérez C, Leng M

Abstract

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.

MeSH Terms
Base Sequence Circular Dichroism Cisplatin/pharmacology Copper Cross-Linking Reagents DNA/chemistry,drug effects Electrophoresis, Polyacrylamide Gel Molecular Sequence Data Nucleic Acid Conformation/drug effects Phenanthrolines
Chemicals
Cross-Linking Reagents Phenanthrolines Copper DNA Cisplatin
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Malinge J M
Centre de Biophysique Moléculaire, CNRS, Orléans, France.
Pérez C
Leng M
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Article Info
Journal
Nucleic acids research
Abbr.
Nucleic Acids Res
ISSN
0305-1048
DOI
10.1093/nar/22.19.3834
Published
1994-09-25
Pages
3834-9
Language
English
Region
England
NLM ID
0411011
PMCID
PMC308377
Subset
IM
External Links
PubMed source DOI: 10.1093/nar/22.19.3834 PMC Full Text View journal details
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