NMR structural studies of the ionizing radiation adduct 7-hydro-8-oxodeoxyguanosine (8-oxo-7H-dG) opposite deoxyadenosine in a DNA duplex. 8-oxo-7H-dG(syn)ter dot dA(anti) alignment at lesion site

Journal Article · Tue Feb 05 00:00:00 EST 1991 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00219a034· OSTI ID:5556220

Kouchakdjian, M; Patel, D J ^[1]; Bodepudi, V; Shibutani, S; Eisenberg, M; Johnson, F; Grollman, A P ^[2]

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1. Columbia Univ., New York, NY (USA)
2. State Univ. of New York, Stony Brook (USA)

Proton NMR studies are reported on the complementary d(C1-C2-A3-C4-T5-A6-oxo-G7-T8-C9-A10-C11-C12){center dot}d(G13-G14-T15-G16-A17-A18-T19-A20-G21-T22-G23-G24) dodecanucleotide duplex (designated 8-oxo-7H-dG{center dot}dA 12-mer), which contains a centrally located 7-hydro-8-oxodeoxyguanosine (8-oxo-7H-dG) residue, a group commonly found in DNA that has been exposed to ionizing radiation or oxidizing free radicals. From the NMR spectra it can be deduced that this moiety exists as two tautomers, or gives rise to two DNA conformations, that are in equilibrium and that exchange slowly. The present study focuses on the major component of the equilibrium that originates in the 6,8-dioxo tautomer of 8-oxo-7H-dG. The authors have assigned the exchangeable NH1, NH7, and NH{sub 2}-2 base protons located on the Watson-Crick and Hoogsteen edges of 8-oxo-7H-dG7 in the 8-oxo-7H-dG{center dot}dA 12-mer duplex, using an analysis of one- and two-dimensional nuclear Overhauser enhancement (NOE) data in H{sub 2}O solution. They were able to detect a set of intra- and interstrand NOEs between protons (exchangeable and nonexchangeable) on adjacent residues in the d(A6-oxo-G7-T8){center dot}d(A17-A18-T19) trinucleotide segment centered about the lesion site that establishes stacking of the oxo-dG7(syn){center dot}dA(anti) pair between stable Watson-Crick dA6{center dot}dT19 and dT8{center dot}A17 base pairs with minimal perturbation of the helix. The structural studies demonstrate that 8-oxo-7H-dG(syn){center dot}dA(anti) forms a stable pair in the interior of the helix, providing a basis for the observed incorporation of dA opposite 8-oxo-7H-dG when readthrough occurs past this oxidized nucleoside base.

• OSTI ID: 5556220
• Journal Information: Biochemistry; (United States), Vol. 30:5; ISSN 0006-2960
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
DNA
BIOLOGICAL RADIATION EFFECTS
DNA ADDUCTS
NUCLEAR MAGNETIC RESONANCE
MOLECULAR STRUCTURE
NMR SPECTRA
OLIGONUCLEOTIDES
RADIOINDUCTION
STEREOCHEMISTRY
ADDUCTS
BIOLOGICAL EFFECTS
MAGNETIC RESONANCE
NUCLEIC ACIDS
ORGANIC COMPOUNDS
RADIATION EFFECTS
RESONANCE
SPECTRA
550601* - Medicine- Unsealed Radionuclides in Diagnostics