CONFORMATIONS OF DNA DUPLEXES CONTAINING 8-OXOGUANINE

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 i n DNA conformational parameters due to mispairs within the sequences d (A(5)XA(5)).d(T5YT5) and d(G(5)XG(5)). 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 confo rmational changes, similar to normal base sequence effects. The calcul ations suggest that both OG(syn): G and OG(syn): A mispairs can also b e introduced without drastic distortion of sugar-phosphate backbone. T he distortion's produced by OG-containing mispairs are also found to b e sequence dependent. Overall these calculations suggest that the G -- > OG conversion could be an important factor in the irradiative or oxi dative damage of DNA.