Abstract
DNA repair pathways have long been recognized as important in protecting the genome from damage caused by endogenous and exogenous DNA damaging agents. However, the role of reduction–oxidation (redox) signaling as a regulatory mechanism in these pathways is a comparatively recent discovery. We have attempted to cover the general aspects of DNA repair, while focusing more attention on the interface between redox regulation and DNA repair activity and response in mammalian cells. The primary focus of this chapter is on APE1, the only DNA repair protein currently known to serve a dual role as a DNA repair enzyme and redox signaling factor. APE1 has been shown to regulate a number of downstream transcription factors (TF) such as HIF-1α, Egr-1, AP-1, NFκB, CREB, p53 and an increasing number of other TFs and other proteins. Additionally, this redox signaling function of APE1 indirectly alters the activity of other DNA repair pathways through its regulation of TF binding to DNA. Included in this chapter is also an overview of general redox systems. We also discuss the role small molecule inhibitors play in the modulation of APE1 redox activity and the potential for chemotherapeutic development via targeting redox regulation of DNA repair.
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