- Oxidative DNA damage is epigenetic by regulating gene transcription via base excision repair.
Oxidative DNA damage is epigenetic by regulating gene transcription via base excision repair.
Proceedings of the National Academy of Sciences of the United States of America (2017-02-02)
Aaron M Fleming, Yun Ding, Cynthia J Burrows
PMID28143930
ABSTRACT
Reactive oxygen species (ROS) have emerged as important cellular-signaling agents for cellular 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-forming sequences (PQS) in promoter-coding strands, initiating 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, adopting a G-quadruplex fold in which apurinic/apyrimidinic endonuclease 1 (APE1) binds, but inefficiently cleaves, the AP for activation of vascular endothelial growth factor (
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