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PubMed · 8751447

Oxidative DNA damage through long-range electron transfer.

D B Hall·R E Holmlin·J K Barton
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Abstract

The possibility has been considered for almost forty years that the DNA double helix, which contains a pi-stacked array of heterocyclic base pairs, could be a suitable medium for the migration of charge over long molecular distances. This notion of high charge mobility is a critical consideration with respect to DNA damage. We have previously found that the DNA double helix can serve as a molecular bridge for photo-induced electron transfer between metallointercalators, with fast rates (> or = 10(10)s-1) and with quenching over a long distance (>40 A). Here we use a metallointercalator to introduce a photoexcited hole into the DNA pi-stack at a specific site in order to evaluate oxidative damage to DNA from a distance. Oligomeric DNA duplexes were prepared with a rhodium intercalator 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 A away from the site of rhodium intercalation. We find that the yield of oxidative damage depends sensitively upon oxidation potential and pi-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 pi-stack.

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Base SequenceDNADNA DamageElectron TransportIntercalating AgentsMolecular Sequence DataOxidation-ReductionPhotolysisRhodiumJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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D B Hall, R E Holmlin, J K Barton. 1996-08-22. Oxidative DNA damage through long-range electron transfer.. https://doi.org/10.1038/382731a0

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