Sugar radicals in irradiated DNA

Another example of the predictive power of theoretical calculations can be found in C3. Through comparison of the two calculated C2 H couplings in the N and S-type conformers with experimental results obtained from 2 -deoxyguanosine 5 -monophosphate (Table 9) [21], the nature of the observed radical is difficult to predict. However, the calculated HFCCs for the N and S-type C3 radicals differ through the absence of a C4 H coupling in the latter conformation. Since a large C4 H coupling was recorded experimentally, the calculations predict this radical to be present in the north conformation. The 

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The poor agreement between theory and experiment cannot always be improved upon by the sole investigation of rotational effects. For exanple, a rotational 

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Close DM (1999) Where are the sugar radicals in irradiated DNA Radiat Res 147 663-673 Close DM (2003) Model calculations of radiation induced damage in DNA constituents using density functional theory. In Leszczynski J (ed) Computational chemistry, reviews of current trends, Vol. 8. World Scentific, Singapore, pp 209-247... 

In single crystals of deoxyadenosine [45], the site of oxidation seems to be the deoxyribose moiety. This brings up an interesting point. In studies of the radiation-induced defects in nucleosides and nucleotides, one often sees evidence of damage to the ribose or deoxyribose moiety. These radicals have not been discussed here because much less is known about sugar-centered radicals in irradiated DNA. 

The guanine moiety has the lowest ionization potential of any of the DNA bases or of the sugar-phosphate backbone. As a result, radiation-produced holes are stabilized as dG for hydrated DNA irradiated at 77 K There is an extensive literature describing the role of dG in the radiation chemistry of DNA as studied by pulse radiolysis, flash photolysis, and product analysis. In order to explicate the oxidative reaction sequence in irradiated DNA and to more firmly identify the relevant radical intermediates, ESR spectroscopy was employed to investigate y-irradiated hydrated DNA (T = 12 2). Some experiments were also performed on hydrated (T = 12 2) DNA in which an electron scavenger [thallium(ni) (TP )] was employed to isolate the oxidative path. Oxygen-17 isotopically enriched water was also used to confirm a proposed water addition step to G and the subsequent transformations that follow These experiments were run in oxygen-free samples under conditions for which indirect effects were unimportant. 

Shukla LI, Pazdro R, Becker D, SeviUa MD. (2005) Sugar radicals in DNA Isolation of neutral radicals in gamma-irradiated DNA by hole and electron scavenging. Radiat Res 167 501-507. 

Some time ago, an allyl-like radical was observed in irradiated crystals of 5 -dCMP [26]. This radical was thought to be a sugar radical, although no likely scheme was proposed for its formation. It now appears that this radical is formed on 5-methyl cytosine impurities in these crystals [27]. This radical forms by deprotonation at the methyl group of the cytosine cation, 5meCyt(Me—H) , and may have important consequences in the radiation chemistry of DNA since the ionization potential of 5-methyl cytosine is lower than that of either cytosine or thymine. 

Becker D, La VereT, Sevilla MD (1994) ESR detection at 77 K of the hydroxyl radical in the hydration layer of gamma-irradiated DNA. Radiat Res 140 123-129 Becker D, Bryant-Friedrich A, Trzasko C-A, Sevilla MD (2003) Electron spin resonance study of DNA irradiated with an argon-ion beam evidence for formation of sugar phosphate backbone radicals. Radiat Res 160 174-185... 

CT, and possible C4 and C5 sugar radicals have been observed in irradiated hydrated DNA at 77K [66], The CT sugar radical was reported by Razskazovskii et al. in a DNA double helix [69]. The C1 was also produced in double stranded DNA at 77 K by photoexcitation of the guanine cation radical [70], The C3 radical was reported to be 4.5% of the total radical yield in the duplex (d(CTCTCGAGAG)), x-irradiated and observed at 4 K [71], It is very likely that the DNA simulations could be improved with the inclusion of a small percentage of these typical sugar radicals. 

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