Oxidative DNA damage is epigenetic by regulating gene transcription via base excision repair

Reactive oxygen species (ROS) have emerged as important cellular signaling agents for survival. Herein, we demonstrate that ROS-mediated oxidation of DNA to yield 8-oxo-7,8-dihydroguanine (OG) in gene promoters is a signaling agent for gene activation. Enhanced gene expression occurs when OG is formed in guanine-rich, potential G-quadruplex sequences (PQS) in promoter coding strands to initiate base excision repair (BER) by 8-oxoguanine DNA glycosylase (OGG1) yielding an abasic site (AP). The AP enables melting of the duplex to unmask the PQS to adopt a G-quadruplex fold in which apurinic/apyrimidinic endonuclease 1 (APE1) binds, but inefficiently cleaves, the AP for activation of VEGF or NT