| Description |
Oxidative damage to DNA, a factor in cancer, mutation, and aging, is attributed to reactive oxygen species (ROS). ROS are formed exogenously and endogenously and attack DNA showing a preference for reaction with 2-deoxyguanosine (dG) sites. In present work, dG was oxidized by HO. that was generated via iron-Fenton reaction or by X-ray radiolysis of water. Under aerobic conditions and in presence of reductant, the product 5-carboxamido-5-formamido-2-iminohydantoin (d2Ih) was the major lesion formed. The above prescribed conditions are mimic to cellular conditions. DNA polymerase and base excision repair processing of 2Ih lesion has been evaluated in this study. 2Ih bears a stereocenter in the base and was found as two diasteromers, (R)-2Ih and (S)-2Ih. Single nucleotide insertion opposite (R)-2Ih and (S)-2Ih in the template strand catalyzed by the DNA polymerases Klenow fragment exo?, DPO4, and Hemo KlenTaq demonstrate these lesions cause point mutations. Specifically, they promote thre |
