Articles written in Journal of Biosciences
Volume 41 Issue 2 June 2016 pp 265-275 Article
The stimulatory effect of the aqueous extract of
Volume 43 Issue 4 September 2018 pp 575-583 Article
5,6-Dihydroxy-5,6-dihydrothymine (thymine glycol) and 7,8-dihydro-8-oxo-20-deoxyguanosine (8-oxodG) are major DNAdamage lesions produced by endogenous oxidative stress, as well as inflicted by carcinogens and ionizing radiation. Theprocessing of Tg:G mismatch and 8-oxodG in close proximity of each other in a bistranded clustered environment in DNAoligomer duplexes as well as in a nucleosome core particle (NCP) model are reported here. The processing of the lesionswas evaluated by purified enzyme cocktails of hNTH1 and hOGG1 as well as with a HeLa cell extract. Interestingly, theyield of double-strand breaks (DSBs) resulting from the processing of the bistranded lesions are appreciably lower when theDNA is treated with the HeLa cell extract compared with the relevant purified enzyme cocktail in both models. Clusteredbistranded lesions become more repair refractive when reconstituted as an NCP. This indicates a complex interplay betweenthe repair enzymes that influence the processing of the bistranded cluster damage positively to avoid the formation of DSBsunder cellular conditions. In addition to position and orientation of the lesions, the type of the lesions in the clusterenvironment in DNA along with the relative abundance of the lesion-specific enzymes in the cells strongly prevents theprocessing of the oxidized nucleobases.