GUANINE IS THE TARGET FOR DIRECT IONIZATION DAMAGE IN DNA, AS DETECTED USING EXCISION ENZYMES

Exposure of an aqueous, aerated solution (pH 7) of a double-stranded D NA to 193 nm light, of sufficient energy to ionise DNA, leads to selec tive, non-random modification at guanine in the form of frank single-s trand break (ssb) and base modifications, revealed by treatment with e ither Escherichia coli formamido-pyrimidine-DNA glycosylase (Fpg), Esc herichia coli endonuclease III (Nth) or hot piperidine treatment, Ther e is a similar neighbouring base sequence dependence for Fpg- and Nth- sensitive damage as that previously reported for both hot alkali-labil e damage and prompt ssb, Low yields of photoproducts, namely pyrimidin e dimers, are also revealed using the enzyme T4 endonuclease V (T4 end o V), Although irradiation of DNA with 193 nm light causes photoionisa tion of all the nucleic acid bases, these results indicate that guanin e is the predominant site for localisation of the oxidative damage. Th ese findings are consistent with migration of the radical cation to 't arget' damage at guanine sites.