Oxidized DNA Base Damage Repair and Transcription: A New Mechanism for Regulation of Gene Expression in Cancer

The DNA bases in the genome are susceptible to oxidation by reactive oxygen species (ROS). The oxidized DNA base lesions such as 8-oxoguanine (8-oxoG) and thymine glycol are primarily repaired by the base excision repair (BER) pathway. Increasing pieces of evidence suggest that oxidative stress-induced base damages in the gene promoter serve as epigenetics marks to regulate gene expression by recruitment of BER proteins. To shed light on this novel role of oxidative DNA base modifications and BER proteins, in this chapter, we focus on how controlled guanine oxidation in gene promoters and BER proteins 8-oxoguanine DNA glycosylase (OGG1) and AP-endonuclease 1 (APE1) regulate expression of multiple genes that drive cancer progression and metastases. Further, we highlight the current studies suggesting a novel role of 8-oxoG and BER in regulating the formation of noncanonical DNA secondary structures such as G-quadruplexes (G4s) to regulate gene expression. Since high oxidative stress in tumor cells creates selective pressure on DNA damage repair pathways to maintain sustained growth, invasion, and metastases via modulating gene expression, such efforts to address the intertwined roles of DNA base modification, BER pathway, and gene expression could broaden cancer-therapeutic strategies.