Guanine modifications following ionization of DNA occurs predominantly viaintra- and not interstrand charge migration: An experimental and theoretical study

A series of double-stranded DNA samples of known sequence were used to asse ss whether 193 nm light induced charge migration in DNA in an aqueous, aera ted 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-D NA glycosylase (Fpg), mainly at guanine with the majority of the DNA sequen ces. If one strand of the DNA contains a guanine poor region, damage also l ocalizes 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 s equence around that site. The experimentally determined distribution of bas e damage has also been compared with that for distribution of charge densit y, simulated using a quantum mechanical model assuming charge migrates alon g either a single strand or either strand of the DNA. In the majority of ca ses, the distribution of charge density using the model assuming intrastran d charge migration and the distribution of Fpg sensitive sites induced by 1 93 nm light are predicted. It is proposed that photoionization of DNA resul ts predominantly in sequence dependent intra- and not interstrand charge mi gration with localization at the most readily oxidized base, generally guan ine.