Document Detail


Interstrand cross-links of cisplatin induce striking distortions in DNA.
MedLine Citation:
PMID:  10626349     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In the reaction between cellular DNA and cisplatin, different bifunctional adducts are formed including intrastrand and interstrand cross-links. The respective role of these lesions in the cytotoxicity of the drug is not yet elucidated. This paper deals with the current knowledge on cisplatin interstrand cross-links and presents results on the formation, stability and structure of these adducts. A key step in the studies of these lesions is the recent determination of solution and crystallographic structures of double-stranded oligonucleotides containing a unique interstrand cross-link. The DNA distortions induced by this adduct exhibit unprecedented features such as the location of the platinum residue in the minor groove, the extrusion of the cytosines of the cross-linked d(GpC).d(GpC) site, the bending of the helix axis towards the minor groove and a large DNA unwinding. In addition to a detailed determination of the distortions, the high resolution of the crystal structure allowed us to locate the water molecules surrounding the adduct. The possible implications of this structure for the chemical properties and the cellular processing of cisplatin interstrand cross-links are discussed.
Authors:
J M Malinge; M J Giraud-Panis; M Leng
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Journal of inorganic biochemistry     Volume:  77     ISSN:  0162-0134     ISO Abbreviation:  J. Inorg. Biochem.     Publication Date:  1999 Oct 
Date Detail:
Created Date:  2000-02-10     Completed Date:  2000-02-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7905788     Medline TA:  J Inorg Biochem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  23-9     Citation Subset:  IM    
Affiliation:
Centre de Biophysique Moléculaire, CNRS, Orléans, France. malinge@cnrs-orleans.fr
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MeSH Terms
Descriptor/Qualifier:
Cisplatin / pharmacology*
Cross-Linking Reagents / chemistry,  pharmacology*
DNA / chemistry,  drug effects*,  genetics
DNA Adducts / chemistry,  drug effects
Female
Humans
Models, Molecular
Nucleic Acid Conformation / drug effects
Pregnancy
Chemical
Reg. No./Substance:
0/Cross-Linking Reagents; 0/DNA Adducts; 15663-27-1/Cisplatin; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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