Guanine Radical Cations Are Precursors of 7,8-Dihydro-8-oxo-2‘-deoxyguanosine But Are Not Precursors of Immediate Strand Breaks in DNA

Abstract

Biphotonic photoionization of frozen aqueous solutions of DNA at 248 nm has been shown by EPR spectroscopy to lead selectively to the guanine cation. In H 2 18 O under these conditions high levels of [ 18 O]-7,8dihydro-8-oxo-2′-deoxyguanosine are produced in a dose-dependent manner, confirming direct formation of this oxidation product by hydration of the guanine cation. Photoionization of defined oligonucleotides did not give rise to significant levels of immediate strand breaks but generated G-specific alkali-labile sites that are readily cleaved by piperidine treatment. Authentic oligonucleotides containing 7,8-dihydro-8-oxo-2′-deoxyguanosine (8-oxodG, 5) sites are slowly cleaved at these sites on treatment with piperidine but at rates inconsistent with this being the source of the alkali-labile site. Photoionization of 7,8-dihydro-8-oxo-2′-deoxyguanosine-containing oligonucleotides demonstrated that this residue is highly susceptible to secondary oxidation and leads to formation of a markedly more alkali-labile lesion. Photoionization of 7,8-dihydro-8-oxo-2′-deoxyguanosine leads to release of 7,8-dihydro-8-oxoguanine suggesting that the alkali-labile site on photoionization of 7,8-dihydro-8-oxo-2′-deoxyguanosinecontaining oligonucleotides is an apurinic site. However, the lack of significant 7,8-dihydro-8-oxoguanine release on photoionization of the parent oligonucleotides rules out secondary oxidation of 7,8-dihydro-8-oxo-2′-deoxyguanosine as the mechanism of formation of alkali-labile sites.

DNA repair glycosylases with a [4Fe–4S] cluster: A redox cofactor for DNA-mediated charge transport?

“…Without MutY, irradiation of poly(dGC), [Ru (phen) 2 dppz] 2+ , and [Co(NH 3 ) 5 Cl] 2+ leads to an EPR signal with g = 2.004. This signal has been previously reported and is assigned to the guanine radical [67]. Irradiation of poly(dGC) in the presence of MutY, however, results in the appearance of new EPR signals with primary g values of 2.02 and 2.08 and a feature at 2.06.…”

Peptide nucleic acid–DNA duplexes: Long range hole migration from an internally linked anthraquinone

“…3) as the trap on this basis. This modified base is often detected as a byproduct of oxidative damage (14,20,23,31,(33)(34)(35)(36). Although structural information is not available for PNA-containing duplexes, Williams and coworkers (37) recently determined the structure of a DNA duplex having an 8-OxoG substitution by x-ray crystallography and found that the oxidized base caused little perturbation.…”

“…Time-resolved spectroscopy reveals that the excited state of the quinone accepts an electron from a base in the DNA within 20 ps of excitation (21). The base radical cation (hole) can either recombine with the electron, be trapped by reaction with water and͞or oxygen, or migrate along the DNA helix to the lowest oxidation potential sites that serve as traps (22,23).…”

“…Time-resolved spectroscopy reveals that the excited state of the quinone accepts an electron from a base in the DNA within 20 ps of excitation (21). The base radical cation (hole) can either recombine with the electron, be trapped by reaction with water and͞or oxygen, or migrate along the DNA helix to the lowest oxidation potential sites that serve as traps (22,23).We prepared a series of PNA oligomers with anthraquinone derivatives (AQ) covalently linked to internal positions. The ability of the quinone to photosensitize DNA damage by electron transfer when bound to the duplex by intercalation suggested it could serve a similar role in PNA-containing duplexes.…”

Kinetic behavior of the reaction between hydroxyl radical and the SV40 minichromosome

“…Guanine bases (E 7 (G(−H) • , H + / G) = +1.29 V, Steenken and Jovanovic 1997) are the most easily oxidized sites in DNA (Colson et al 1992), but the methylperoxyl radical is able to oxidize them only to a minor extent (Milligan et al 1996). Since oxidation products of guanine bases do not produce SSBs under the conditions we have used here (Cullis et al 1996), this reaction may be safely ignored. Redox active amino acids present in the histone proteins of the SV40 minichromosome such as tyrosine (E 7 = +0.93 V, Harriman 1987;DeFilippis et al 1989) and tryptophan (E 7 = +1.03 V, Harriman 1987; Wardman 1989) may be oxidized more extensively by the methylperoxyl radical.…”