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Nucleic Acids Research, Vol 26, Issue 21 4935-4942, Copyright © 1998 by Oxford University Press

ARTICLES

Guanine is the target for direct ionisation damage in DNA, as detected using excision enzymes

T Melvin, SM Cunniffe, P O'Neill, AW Parker and T Roldan-Arjona
MRC Radiation and Genome Stability Unit, Harwell, OX11 ORD, UK. melvin@cnrs-orleans.fr

Exposure of an aqueous, aerated solution (pH 7) of a double-stranded DNA to 193 nm light, of sufficient energy to ionise DNA, leads to selective, non-random modification at guanine in the form of frank single-strand break (ssb) and base modifications, revealed by treatment with either Escherichia coli formamidopyrimidine-DNA glycosylase (Fpg), Escherichia coli endonuclease III (Nth) or hot piperidine treatment. There is a similar neighbouring base sequence dependence for Fpg- and Nth-sensitive damage as that previously reported for both hot alkali- labile damage and prompt ssb. Low yields of photoproducts, namely pyrimidine dimers, are also revealed using the enzyme T4 endonuclease V (T4 endo V). Although irradiation of DNA with 193 nm light causes photoionisation of all the nucleic acid bases, these results indicate that guanine is the predominant site for localisation of the oxidative damage. These findings are consistent with migration of the radical cation to 'target' damage at guanine sites.
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