SYMMETRY REDUCTION IN HOMOPOLYMERIC DNA - IMPLICATIONS FOR DNA FINE-STRUCTURE

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Conformations of DNA duplexes containing 8-oxoguanine.

International audienceAs a step towards elucidating the mechanisms of mutagenesis induced by irradiation and oxidation, we study the incorporation of 8-oxoguanine (OG) into duplex DNA. Molecular modelling is used to reveal changes in DNA conformational parameters due to mispairs within the sequences d(A5XA5).d(T5YT5) and d(G5XG5).d(C5YC5) where one of the bases of the bases of the central X:Y pair is OG and the other A,T,G or C. The G:C to OG:C replacements in DNA duplexes produce only minor conformational changes, similar to normal base sequence effects. The calculations suggest that both OG(syn):G and OG(syn):A mispairs can also be introduced without drastic distortion of sugar-phosphate backbone. The distortions produced by OG-containing mispairs are also found to be sequence dependent. Overall these calculations suggest that the G-->OG conversion could be an important factor in the irradiative or oxidative damage of DNA.As a step towards elucidating the mechanisms of mutagenesis induced by irradiation and oxidation, we study the incorporation of 8-oxoguanine (OG) into duplex DNA. Molecular modelling is used to reveal changes in DNA conformational parameters due to mispairs within the sequences d(A5XA5).d(T5YT5) and d(G5XG5).d(C5YC5) where one of the bases of the bases of the central X:Y pair is OG and the other A,T,G or C. The G:C to OG:C replacements in DNA duplexes produce only minor conformational changes, similar to normal base sequence effects. The calculations suggest that both OG(syn):G and OG(syn):A mispairs can also be introduced without drastic distortion of sugar-phosphate backbone. The distortions produced by OG-containing mispairs are also found to be sequence dependent. Overall these calculations suggest that the G-->OG conversion could be an important factor in the irradiative or oxidative damage of DNA

A DFT study of uracil and 5-bromouracil in nanodroplets

The canonical (keto) and rare (enol) tautomers of uracil and 5-bromouracil in clusters comprising 50 and 100 water molecules (nanodroplets) were studied using density functional theory. The geometries of the various complexes were optimized at two different levels of theory, BLYP/6-31G(d,p) and B3LYP/6-31G(d,p). Tautomerization energies were computed using the BLYP, B3LYP and M05-2X density functionals. The gas-phase tautomerization energies of uracil and 5-bromouracil are very similar, favoring the keto tautomer. However, in the hydrated phase, the tautomeric preference of 5-bromouracil is reversed. This result is obtained for all four sets of clusters (BLYP or B3LYP optimized, containing 50 or 100 water clusters) and at all levels of theory employed, and indicates that a bromine atom in the 5-position considerably increases the proportion of the hydroxyl group present in uracil.</p