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Titolo:
INFLUENCE OF THE OXIDATIVELY DAMAGED ADDUCT 8-OXODEOXYGUANOSINE ON THE CONFORMATION, ENERGETICS, AND THERMODYNAMIC STABILITY OF A DNA DUPLEX
Autore:
PLUM GE; GROLLMAN AP; JOHNSON F; BRESLAUER KJ;
Indirizzi:
RUTGERS STATE UNIV,DEPT CHEM NEW BRUNSWICK NJ 08903 SUNY STONY BROOK,DEPT PHARMACOL SCI STONY BROOK NY 11794
Titolo Testata:
Biochemistry
fascicolo: 49, volume: 34, anno: 1995,
pagine: 16148 - 16160
SICI:
0006-2960(1995)34:49<16148:IOTODA>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
DOUBLE-HELIX FORMATION; ESCHERICHIA-COLI; 8-HYDROXYGUANINE 7,8-DIHYDRO-8-OXOGUANINE; IONIZING-RADIATION; SINGLE 8-OXOGUANINE; MELTING CURVES; PURINE-BASES; HUMAN-CELLS; MUTY GENE; MUTAGENESIS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
71
Recensione:
Indirizzi per estratti:
Citazione:
G.E. Plum et al., "INFLUENCE OF THE OXIDATIVELY DAMAGED ADDUCT 8-OXODEOXYGUANOSINE ON THE CONFORMATION, ENERGETICS, AND THERMODYNAMIC STABILITY OF A DNA DUPLEX", Biochemistry, 34(49), 1995, pp. 16148-16160

Abstract

As part of an overall program to characterize the impact of mutageniclesions on the physiochemical properties of DNA, we report here the results of a comparative spectroscopic and calorimetric study on a family of DNA duplexes both with and without the oxidative lesion 2'-deoxy-7-hydro-8-oxoguanosine (8-oxodG). Specifically, we have studied a family of eight 13-mer duplexes of the form [5'-GCGTAC[G or G]CATGCG-3'].[3'-CGCATG[C, A, T, or G]GTACGC-5'] in which G is the 8-oxodG lesion. These eight duplexes, which we designate by the identity of the variable central base pair (e.g., GC), reflect two subsets: four duplexesin which the modified guanine base is positioned opposite each of thefour possible canonical residues (GC, G*A, G*G, G*T) and the corresponding four ''control'' duplexes in which the guanine is not modified (GC, GA, GG, GT). The data derived from our spectroscopic and calorimetric measurements on these eight duplexes allow us to evaluate the influence of the 8-oxode lesion, as well as the base opposite the lesion,on the conformation, the thermal and thermodynamic stability, and themelting thermodynamics of the host DNA duplex. We find that modification of dG to 8-oxodG (G) does not change the global DNA duplex conformation as judged by circular dichroism spectra. Despite this structural similarity, our data reveal that the dG to dG modification does influence duplex thermal and thermodynamic properties, some of which depend on the base opposite the lesion. Thus, apparent structural identitydoes not mean that two duplexes necessarily will exhibit equivalent thermal and/or thermodynamic properties. In general, we find that the thermodynamic effects induced by the lesion (e.g., GC vs GC) or by mismatched base pairs (e.g., GC vs GC) can result in relatively large changes in enthalpy which are partially or wholly compensated entropically to produce relatively modest changes in free energy. Our data also suggest that the biologically observed differential recognition of 8-oxodG duplexes and the preferential nucleotide insertion opposite 8-oxodG residues cannot be rationalized simply in terms of large thermodynamic differences.

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Documento generato il 07/07/20 alle ore 11:09:45