Single 8-oxo-guanine and 8-oxo-adenine lesions induce marked changes in the backbone structure of a 25-base DNA strand

Structural changes in a 25-base DNA strand, induced by single 8-oxo-guanine or 8-oxo-adenine substitutions, were shown by using Fourier transform-infr ared spectroscopy with multivariate statistics. Pronounced differences were demonstrated between the parent and derivatives with respect to base inter actions and changes in the phospho-deoxyribose backbone. The greatest degre e of change in the backbone likely occurred immediately adjacent to the 8-o xo group, potentially altering the stereochemistry at a distance. The 8-oxo lesions, formed from reactive oxygen species (e.g.. hydroxyl radicals), ma y appreciably alter the conformational properties of strands at the replica tion fork, thus affecting the selectivity of polymerases. the proofreading capability of repair enzymes, and the fidelity of the transcriptional machi nery.