RT Journal Article SR Electronic T1 Oxidative DNA damage is epigenetic by regulating gene transcription via base excision repair JF bioRxiv FD Cold Spring Harbor Laboratory SP 069955 DO 10.1101/069955 A1 Aaron M. Fleming A1 Yun Ding A1 Cynthia J. Burrows YR 2016 UL http://biorxiv.org/content/early/2016/08/17/069955.abstract AB 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 NTHL1 genes. This concept allowed identification of 61 human DNA repair genes that might be activated by this mechanism. Identification of the oxidatively-modified DNA base OG as guiding protein activity on the genome and altering cellular phenotype ascribes an epigenetic role to OG.