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Oxidative DNA damage through long-range electron transfer


THE possibility has been considered for almost forty years that the DNA double helix, which contains a π-stacked array of heterocyclic base pairs, could be a suitable medium for the migration of charge over long molecular distances1–11. This notion of high charge mobility is a critical consideration with respect to DNA damage. We have previously found7–10 that the DNA double helix can serve as a molecular bridge for photo-induced electron transfer between metallointercalators, with fast rates (≥1010 S−1)10 and with quenching over a long distance (>40Å)8. Here we use a metallointercalator to introduce a photoexcited hole into the DNA π-stack at a specific site in order to evaluate oxidative damage to DNA from a distance. Oligomeric DNA duplexes were prepared with a rhodium inter-calator covalently attached to one end and separated spatially from 5′-GG-3′ doublet sites of oxidation. Rhodium-induced photo-oxidation occurs specifically at the 5′-G in the 5′-GG-3′ doublets and is observed up to 37 Å away from the site of rhodium intercalation. We find that the yield of oxidative damage depends sensitively upon oxidation potential and π-stacking, but not on distance. These results demonstrate directly that oxidative damage to DNA may be promoted from a remote site as a result of hole migration through the DNA π-stack.

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Hall, D., Holmlin, R. & Barton, J. Oxidative DNA damage through long-range electron transfer. Nature 382, 731–735 (1996).

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