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 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.
Hall
D B
DB
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena 91125, USA.
Holmlin
R E
RE
Barton
J K
JK
D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D004249:DNA Damage; D004579:Electron Transport; D007364:Intercalating Agents; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010782:Photolysis; D012238:Rhodium
D007364:Intercalating Agents; D004247:DNA; D012238:Rhodium