7,8-Dihydro-8-oxoguanine

Fig. 1 Schematic mechanism for the long-distance oxidation of DNA. Irradiation of the anthraquinone (AQ) and intersystem crossing (ISC) forms the triplet excited state (AQ 3), which is the species that accepts an electron from a DNA base (B) and leads to products. Electron transfer to the singlet excited state of the anthraquinone (AQ 1) leads only to back electron transfer. The anthraquinone radical anion (AQ ) formed in the electron transfer reaction is consumed by reaction with oxygen, which is reduced to superoxide. This process leaves a base radical cation (B+-, a hole ) in the DNA with no partner for annihilation, which provides time for it to hop through the DNA until it is trapped by water (usually at a GG step) to form a product, 7,8-dihydro-8-oxoguanine (8-OxoG)...

Fig. 4 Schematic representation of long-distance radical cation migration in DNA. In AQ-DNA(l), irradiation of the anthraquinone group linked at the 5 -terminus leads to reaction at GG steps that are 27 A and 44 A from the site of charge injection. The amount of reaction observed at each guanine is represented approximately by the length of the solid arrow. In UAQ-DNA(2), irradiation of the anthraquinone leads to reaction at each of the eight GG steps. However, replacement of a G by 7,8-dihydro-8-oxoguanine (8-OxoG) introduces a deep trap that inhibits reaction at guanines on the same side of the DNA as the trap...

Another source of modified bases in both DNA and RNA is spontaneous or "accidental" alteration. Nucleic acids encounter many highly reactive and mutagenic materials including hydroxyl radicals, formed from 02, and are able to convert guanine rings into 7,8-dihydro-8-oxoguanine.362 Other reactive and carcinogenic compounds can form adducts with nucleic acid bases.363 See Eq. 5-18 and also Chapter 27. 

Both NER and BER forms of excision repair remove a great variety of defects, many of which are a result of oxidative damage.657 720 Most prominent among these is 7,8-dihydro-8-oxoguanine (8-OG), which is able to base pair with either cytosine (with normal Watson-Crick hydrogen bonding) or with adenine, which will yield a purine-purine mismatch and aC G —> A T transversion mutation (Eq. 27-24), a frequent mutation in human cancers.721 722... 

The nucleobase analogue 7,8-dihydro-8-oxoguanine (OG Figure lb) is of particular interest as a likely intermediate in the oxidation of guanine [6, 7], Calculations by Prat et al. [39] indicate that the IP of OG is c. 0.4 eV lower than that of G. Stacking of OG with guanine (either 3 or 5 ) results in a further decrease in the IP of OG. 

Bjords M, Luna L, Johnsen B et al. (1997) Opposite base-dependent reactions of a human base excision repair enzyme on DNA containing 7,8-dihydro-8-oxoguanine and abasic sites. EMBO J 16 6314-22... 

M. (2002) Oxidation of 7,8-dihydro-8-oxoguanine affords lesions that are potent sources of replication errors in vivo. Biochemistry, 41, 914-921. 

Haracska, L., Prakash, S., and Prakash, L. (2003) Yeast DNA polymerase t, is an efficient extender of primer ends opposite from 7,8-dihydro-8-oxoguanine and 06-methylguanine. Mol. Cell. Biol., 23, 1453-1459. 

Carlson, K.D. and Washington, M.T. (2005) Mechanism of efficient and accurate nucleotide incorporation opposite 7,8-dihydro-8-oxoguanine by Saccharomyces cerevisiae DNA polymerase ip Mol. Cell. Biol, 25, 2169-2176. 

Fig. 13 Reaction of hydroxyl radicals (HO ) with guanine residues of DNA to form the molecular lesion 7-8,dihydro-8-oxoguanine (8-oxoguanine). If not repaired, this oxidative damage can cause mutations and/or altered gene transcription, which may lead to cancCT and/or canbiyopathies (from Wells et al. 2009)...

Scheme 12a-d. C-H - 0 hydrogen bonds in a Watson-Crick U A pair b Hoogsteen T A pair c 08G-A pair (08G 7,8-dihydro-8-oxoguanine) d Hoogsteen C G pair. For patterns a, b and c, see [57] pattern d is putative... 

Girard, P. M., Guibourt, N., and Boiteux, S. (1997). The Oggl protein of Saccharomyces cerevisiae A 7,8-dihydro-8-oxoguanine DNA glycosylase/AP lyase whose lysine 241 is a critical residue for catalytic activity. Nucleic Adds Res. 25, 3204-3211. 

Henderson, P. T. Delaney, J. C. Muller, J. G. Neeley, W. L. Tannenbaum, S. R. Burrows, C. J. Essigmann, J. M. The hydantoin lesions formed from oxidation of 7,8-dihydro-8-oxoguanine are potent sources of replication errors in vivo. Biochemistry 2003,42, 9257-9262. 

Wood, M.L., Esteve, A., Morningstar, M.L., Kuziemko, G.M., Essigmann, J.M. (1992). Genetic effects of oxidative DNA damage comparative mutagenesis of 7,8-dihydro-8-oxoguanine and 7,8-dihydro-8-oxoadenine in Escherichia coli. Nucleic Acids Res. 20, 6023-6032. 

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