화학공학소재연구정보센터
Nature, Vol.382, No.6593, 731-735, 1996
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(1-11). This notion of high charge mobility is a critical consideration with respect to DNA damage. We have previously found(7-10) that the DNA double helix can serve as a molecular bridge for photo-induced electron transfer between metallointercalators, with fast rates (greater than or equal to 10(10) s(-1))(10) and with quenching over a long distance (>40 Angstrom)(8). Here we use a metallointercalator to introduce a photoexcited hole into the DNA pi-stacked 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 Angstrom 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.