Clustered damage

Modeling and calculations show that with increasing LET, there is a shift toward a greater complexity of clustered damage in DNA [30,81,87,119]. 

Low-energy electrons are efficient in producing clustered damage at DNA level [115]. 

Table12.11. Yieldsofba se damage per SSB and non-DSB clustered damage per DSB, measured in plasmid DNA. (Gulston et al. 2002)...

Clustered lesions are also apparent when DNA films are subjected to y-radia-tion (Yokoya et al. 2002). Here, additional DSBs are at least twice that of prompt DSBs. In contrast, enzymatic treatment of DNA films by a-radiation does not raise the number of DSBs, and it has been suggested that in this case the complexity of the clustered damage may be greater than that formed upon y-radia-tion and that the enzymes can no longer adequately work on such sites (Yokoya et al. 2003). 

David-Cordonnier M-H, Boiteux S, O Neill P (2001a) Efficiency of excision of 8-oxo-guanine within DNA clustered damage by XRS5 nuclear extracts and purified human OGGI protein. Biochemistry 40 11881-11818... 

Goldberg IH (1991) Mechanism of neocarzinostatin action role of DNA microstructure in determination of chemistry of bistranded oxidative damage. Acc Chem Res 24 191-198 Goodhead DT (1994) Initial events in the cellular effect of the ionizing radiations clustered damage in DNA. Int J Radiat Biol 65 7-17... 

Yokoya A, Cunniffe SMT, O Neill P (2002) Effect of hydration on the induction of strand breaks and base lesions in plasmid DNA films by y-radiation.J Am Chem Soc 124 8859-8866 Yokoya A, Cunniffe SMT, Stevens DL, O Neill P (2003) Effect of hydration on the induction of strand breaks, base lesions and clustered damage in DNA films by a-radiation. J Phys Chem B 107 832-837... 

Sutherland B.M., Bennet P.V., Sidorkina 0., Laval J., Clustered damage and total lesions induced in DNA by ionizing radiation oxidized bases and strand breaks. Biochemistry, 2000,39,8026-8031. 

The main oxidation reactions of the 2-deoxyribose of DNA are mediated by "OH that are able to abstract hydrogen atoms from most of the positions with the exception of the methylene group at C2, which is a poorly reactive site [12, 14, 112], An abundant literature is available on the degradation pathways that are derived from the reactions of osidic carbon-centered radicals and that lead in most cases to the formation of strand breaks [12, 14, 112], However, there is one major exception that concerns the chemical reactions of the CT radical that is the precursor of 2-deoxyribonolactone [113]. Here, emphasis is placed on reactions of C4 and C5 radicals that may lead to the formation of base modifications either as tandem lesions or clustered damage. 

CunnifFe S, O Neill P, Greenberg MM, Lomax ME. Reduced repair capacity of a DNA clustered damage site comprised of 8-oxo-7,8-dihydro-2 -deoxyguanosine and 2-deoxyribonolactone results in an increased mutagenic potential of these lesions. Mutat Res Fundam Mol Mech Mutagen. 2014 762 32-39. 

---