Sugar Radicals in DNA

Adhikary A, Malkhasian AYS, Collins S, Koppen J, Becker D, Sevilla MD. (2005) UVA-visible photo-excitation of guanine radical cations produces sugar radicals in DNA and model structures. Nucleic Acids Res 33 5553-5564. 

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. 

The role of sugar radicals in DNA radiation damage is uncertain since no sugar radicals were identified in preliminary studies on fiill DNA samples [42]. 

More recently, this same group has studied DNA with high-field EPR (245 GHz) [51]. This study shows nice spectra of the Thy(Me—H) radical. Also, the authors discuss the effects of hydration levels on the production of the various base radicals. A more recent paper by Weiland and Hiittermann [52] considers the same base radicals in DNA at 77 K and then looks at the transformation of these radicals into the more stable room-temperature products. Among these are Cl and C3 sugar radicals, dRib(Cl —H), and dRib(C3 -H) , respectively. 

The various ways of forming OH were discussed in Chapter 2. It is a very reactive, electrophilic (9 = -0.41 Anbar et al. 1966a) radical, and with most substrates it reacts at close to diffusion-controlled rates (for a compilation of rate constants, see Buxton et al. 1988). It undergoes mainly three types of reactions (1) addition to C-C and C-N double bonds, (2) H-abstraction and (3) ET. Addition and H-abstraction reactions will be discussed below in some detail, because they are relevant for an OH-attack at the nucleobases and at the sugar moiety in DNA. 

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... 

The redox dependence of hydrogen abstraction from sugars by base/nitro-arene radical-adducts (nitroxyl radicals) in DNA has not yet been characterized, and it is quite possible that nitroarenes form adducts at both base and sugar sites. A detailed molecular understanding of the mechanisms of radiosensitization of hypoxic cells therefore remains elusive. For a complete picture it will be necessary to include an appreciation of the structure and accessibility of the target sites. 

Oxygen radicals, in the presence of metal ions such as Fe, can destroy sugar rings in DNA, breaking the strand. 

In some circumstances, DNA radical lesions can react with an adjacent base or the sugar residues. In these cases, a single radical hit can be transformed into two adjacent damage sites on the DNA. The resulting tandem lesions may present special challenges to DNA replication and repair systems. ... 

Fig. 10 Two schematic representations of a polaron-like species in DNA. In the top drawing, the base pairs of DNA are represented by the horizontal lines the sugar diphosphate backbone is represented by the vertical lines. The polaronic distortion is enclosed in the box and extends over some number of base pairs. This is shown schematically by drawing the base-pair lines closer together. In the lower figure, a specific potential po-laron is identified, AAGGAA, and the radical cation is presented as being delocalized over this sequence. Movement of the polaron from one AAGGAA sequence to the next requires thermal activation...

It is well-known that many organic excited states (e.g. the triplet state of benzophenone) can effectively abstract hydrogen atoms from organic compounds such as alkanes and alcohols. This behaviour is not commonly found for metal-containing compounds - a notable exception being the lowest excited state of uranyl ion which abstracts H atoms from alcohols, sugars etc., with the resultant formation of free radicals and U(V) compounds. Recent work has shown that it is very effective in inducing strand breaks in DNA (see Sect. 8). 

About 20% of the HO radicals interact with the sugar phosphate by H-atom abstraction and about 80% react by addition to the nucleobases. In model sugar compounds, the H abstraction would occur evenly between the hydrogens on Cl, C2, C3, C4, and C5. In DNA, H abstraction occurs mainly at C4 since the C4 -H is in the minor groove and to some extent with the C5 -H2. 

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