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Titolo:
DNA sequence context modulates the impact of a cisplatin 1,2-d(GpG) intrastrand cross-link an the conformational and thermodynamic properties of duplex DNA
Autore:
Pilch, DS; Dunham, SU; Jamieson, ER; Lippard, SJ; Breslauer, KJ;
Indirizzi:
Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pharmacol, Piscataway, NJ 08854 USA Univ Med & Dent New Jersey Piscataway NJ USA 08854scataway, NJ 08854 USA Canc Inst New Jersey, New Brunswick, NJ 08901 USA Canc Inst New Jersey New Brunswick NJ USA 08901 w Brunswick, NJ 08901 USA MIT, Dept Chem, Cambridge, MA 02139 USA MIT Cambridge MA USA 02139MIT, Dept Chem, Cambridge, MA 02139 USA Rutgers State Univ, Dept Chem, Piscataway, NJ 08854 USA Rutgers State Univ Piscataway NJ USA 08854 Chem, Piscataway, NJ 08854 USA
Titolo Testata:
JOURNAL OF MOLECULAR BIOLOGY
fascicolo: 3, volume: 296, anno: 2000,
pagine: 803 - 812
SICI:
0022-2836(20000225)296:3<803:DSCMTI>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
ANTICANCER DRUG CISPLATIN; EQUILIBRIUM MELTING CURVES; CIS-DIAMMINEDICHLOROPLATINUM(II) INDUCED DISTORTION; ORDER-DISORDER TRANSITIONS; HMG-DOMAIN; EXCISION NUCLEASE; CRYSTAL-STRUCTURE; BASE SEQUENCE; ABASIC LESION; MAJOR ADDUCT;
Keywords:
differential scanning calorimetry; cisplatin cross-link-induced conformational change; duplex melting cooperativity; protein recognition of platinated DNA; DNA bending;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Pilch, DS Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pharmacol, 675 Hoes Lane, Piscataway, NJ 08854 USA Univ Med & Dent New Jersey675 Hoes Lane Piscataway NJ USA 08854
Citazione:
D.S. Pilch et al., "DNA sequence context modulates the impact of a cisplatin 1,2-d(GpG) intrastrand cross-link an the conformational and thermodynamic properties of duplex DNA", J MOL BIOL, 296(3), 2000, pp. 803-812

Abstract

The anticancer activity of cisplatin derives from its ability to bind and cross-link DNA, with the major adduct being the 1,2-d(GpG) intrastrand cross-link. Here, the consequences of this adduct on the conformation thermal stability, and energetics of duplex DNA are assessed, and the modulation of these parameters by the sequence context of the adduct is evaluated. The properties of a family of 15-mer DNA duplexes containing a single 1,2-d(GpG) cis-{Pt(NH3)(2)}(2+) intrastrand cross-link are probed in different sequence contexts where the flanking base-pairs are systematically varied from T . A to C . G to A . T. By using a combination of spectroscopic and calorimetric techniques, the structural, thermal, and thermodynamic properties of each duplex, both with and without the cross-link, are characterized. Circular dichroism spectroscopic data reveal that the cross-link alters the structure of the host duplex in a manner consistent with a shift from a B-like toan A-like conformation. Thermal denaturation data reveal that the cross-link induces substantial thermal and thermodynamic destabilization of the host duplex. Significantly, the magnitudes of these cross-link-induced effectson duplex structure, thermal stability, and energetics are influenced by the bases that flank the adduct. The presence of flanking AT base-pairs, relative to T-A or C G base-pairs, enhances the extent of cross-link-induced alteration to an Alike conformation and dampens the extent of cross-link-induced duplex destabilization. These results are discussed in terms of available structural data, and in terms of the selective recognition of cisplatin-DNA adducts by HMG-domain proteins. (C) 2000 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/09/20 alle ore 11:40:38