Guanine modifications following ionization of DNA occurs predominantly via intra- and not interstrand charge migration: An experimental and theoretical study
O'Neill P., Parker AW., Plumb MA., Siebbeles LDA.
A series of double-stranded DNA samples of known sequence were used to assess whether 193 nm light induced charge migration in DNA in an aqueous, aerated solution occurs predominantly by inter- or intrastrand processes. Light of 193 nm induces a nonrandom distribution of prompt single strand breaks and base modifications, revealed by Escherichia coli formamido-pyrimidine-DNA glycosylase (Fpg), mainly at guanine with the majority of the DNA sequences. If one strand of the DNA contains a guanine poor region, damage also localizes nonrandomly at adenine, even though a guanine is present within 1-2 base pairs but on the complementary strand. The yield of damage at double guanine (-GG-) sites is greater than at single guanine sites although the specific guanine damage in a -GG- site depends significantly on the local sequence around that site. The experimentally determined distribution of base damage has also been compared with that for distribution of charge density, simulated using a quantum mechanical model assuming charge migrates along either a single strand or either strand of the DNA. In the majority of cases, the distribution of charge density using the model assuming intrastrand charge migration and the distribution of Fpg sensitive sites induced by 193 nm light are predicted. It is proposed that photoionization of DNA results predominantly in sequence dependent intra- and not interstrand charge migration with localization at the most readily oxidized base, generally guanine.