The sacrificial role of easily oxidizable sites in the protection of DNA from damage

Abstract

It has been suggested that DNA contains sacrificial nucleobase sequences that protect sensitive regions of the genome from oxidative damage. Oxidation of DNA by loss of an electron generates a radical cation that can migrate long distances by hopping. The radical cation can be trapped irreversibly at certain sites (GG steps) by reaction with H2O or O2 leading to the formation of lesions (oxidative damage). A series of DNA oligomers that contain regularly spaced GG steps and an 8-oxo-7,8-dihydroguanine (8-oxoG), which serves as a proxy for possibly sacrificial protective low oxidation potential sites, was prepared and analyzed. We find that in certain special sequences of DNA nucleobases that 8-oxoG protects remote GG steps from oxidative damage but that this is not a general phenomenon extending to normal mixed sequence DNA. This is a consequence of the change in the relative rate of charge hopping compared with trapping of the radical cation. When hopping is relatively slow, 8-oxoG exerts no protective effect. Thus, it seems unlikely that low oxidation potential sequences play a meaningful part in protecting mixed sequence DNA from damage. © The Author 2005. Published by Oxford University Press. All rights reserved.