Effects of Oxidative Damage on the Stability and Processing of H-DNA

Genetic instability is known to contribute to cancer and other diseases. DNA can adopt non-B-DNA conformations such as H-DNA, a three-stranded structure found in mutagenic hotspot sequences. Error-prone repair pathways recognize and process H-DNA, leading to large deletions and thereby contributing to genetic instability. Similarly, oxidative damage caused by reactive oxygen species (ROS) can cause mutations leading to modified bases such as 8-oxoguanine (8-oxoG) and abasic sites. We hypothesize that the structural features of H-DNA make it more susceptible to DNA damage by ROS compared to the control B-DNA. The objective of this research is to determine the effects of ROS-induced DNA damage on the mutagenic potential and structural stability of H-DNA. In this study, mutation spectra were analyzed to determine how oxidative damage affects the repair pathway processing of H-DNA. Furthermore, single 8oxoG or abasic lesions were positioned at different locations within a three-stranded foldback DNA structure to evaluate the effects of oxidative damage on the stability of H-DNA.