Direct observation of radical intermediates in protein-dependent DNA charge transport

Charge migration through the DNA base stack has been probed both spectrosco pically, to observe the formation of radical intermediates, and biochemical ly, to assess irreversible oxidative DNA damage. Charge transport and radic al trapping were examined in DNA assemblies in the presence of a site-speci fically bound methyltransferase HhaI mutant and an intercalating ruthenium photooxidant using the flash-quench technique. The methyltransferase mutant , which can flip out a base and insert a tryptophan side chain within the D NA cavity, is found to activate long-range hole transfer through the base p air stack. Protein-dependent DNA charge transport is observed over 50 Angst rom with guanine radicals formed > 10(6) s(-1): hole transport through DNA over this distance is not rate-limiting. Given the time scale and distance regime, such protein-dependent DNA charge transport chemistry requires cons ideration physiologically.