This chapter focuses on the role of apurinic/apyrimidinic endonuclease (APE1) in redox regulation and response to oxidative stress and recent therapeutic developments targeting APE1's redox function. A key enzyme in BER, APE1,6 recognizes a basic sites produced either spontaneously or through removal of an oxidized base by a DNA glycosylase. Knock-out of APE1 in mice is embryonic lethal establishing APE1 as an essential enzyme; 7 APE1 functions in base excision repair by cleaving the phosphodiester backbone 5' of a basic site resulting in a 3'OH and 5' deoxyribose phosphate. Further processing by DNA polymerase beta and DNA ligase completes the DNA repair. APE1 is also a nuclear redox factor that recognizes oxidized transcription factors and reduces them, significantly stimulating their DNA-binding properties. In this regard, APE1 plays a unique role in that it repairs both oxidized DNA and a number of transcription factors, which in turn regulate expression of DNA repair genes.
|Original language||English (US)|
|Title of host publication||DNA Repair in Cancer Therapy|
|Number of pages||21|
|State||Published - Dec 1 2012|
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