OXIDATIVE DNA-DAMAGE THROUGH LONG-RANGE ELECTRON-TRANSFER

The possibility has been considered for almost forty years that the DN A double helix, which contains a pi-stacked array of heterocyclic base pairs, could be a suitable medium for the migration of charge over lo ng 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, wit h fast rates (greater than or equal to 10(10) s(-1))(10) and with quen ching over a long distance (>40 Angstrom)(8). Here we use a metalloint ercalator to introduce a photoexcited hole into the DNA pi-stacked at a specific site in order to evaluate oxidative damage to DNA from a di stance. Oligomeric DNA duplexes were prepared with a rhodium intercala tor 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 t o 37 Angstrom away from the site of rhodium intercalation. We find tha t the yield of oxidative damage depends sensitively upon oxidation pot ential and pi-stacking, but not on distance. These results demonstrate directly that oxidative damage to DNA may be promoted from a remote s ite as a result of hole migration through the DNA pi-stack.