Solution structure of a cisplatin-induced DNA interstrand cross-link.
Science
; 270(5243): 1842-5, 1995 Dec 15.
Article
en En
| MEDLINE
| ID: mdl-8525382
The widely used antitumor drug cis-diamminedichloroplatinum(II) (cisplatin or cis-DDP) reacts with DNA, cross-linking two purine residues through the N7 atoms, which reside in the major groove in B-form DNA. The solution structure of the short duplex [d(CAT-AGCTATG)]2 cross-linked at the GC:GC site was determined by nuclear magnetic resonance (NMR). The deoxyguanosine-bridging cis-diammineplatinum(II) lies in the minor groove, and the complementary deoxycytidines are extrahelical. The double helix is locally reversed to a left-handed form, and the helix is unwound and bent toward the minor groove. These findings were independently confirmed by results from a phase-sensitive gel electrophoresis bending assay. The NMR structure differs markedly from previously proposed models but accounts for the chemical reactivity, the unwinding, and the bending of cis-DDP interstrand cross-linked DNA and may be important in the formation and repair of these cross-links in chromatin.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
ADN
/
Cisplatino
/
Antineoplásicos
/
Conformación de Ácido Nucleico
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Science
Año:
1995
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos