Figure 2: The dual functions of APE1/Ref-1. As a DNA repair protein, APE1/Ref-1 functions as the primary enzyme responsible for recognition and repair of mutagenic apurinic/apyrimidinic (AP) sites in DNA as part of the base excision repair (BER) pathway. As a redox protein, APE1/Ref-1 functions as an activator of transcription factors involved in multiple cellular processes, including AP-1, p53, NF-κB, HIF-1α, and others. Activation involves the reduction of a cysteine residue to a sulfhydryl state. Dietary agents may target APE1/Ref-1 DNA repair or redox activities or both, causing multiple downstream effects.