APE1

APE1, also known as Ref-1 (redox effector factor 1), is a multifunctional enzyme in mammalian cells that participates in base excision repair and redox regulation of transcription factors. It is encoded by the APEX1 gene in humans and is widely expressed in tissues.

In base excision repair, APE1 recognizes abasic (apurinic/apyrimidinic) sites that arise from DNA damage and cleaves the phosphodiester backbone 5' to the site. This cleavage generates a 3'-hydroxyl and a 5'-deoxyribose phosphate, creating entry points for downstream BER enzymes such as DNA polymerase beta and DNA ligase to complete the repair. APE1 also possesses 3'-phosphodiesterase and 3'-phosphatase activities that help remove obstructive DNA ends, facilitating proper repair synthesis.

Beyond its repair function, APE1 has a redox regulatory activity as Ref-1. It reduces oxidized cysteine residues in various transcription factors, including AP-1, NF-κB, HIF-1α, and p53, thereby modulating their DNA-binding affinity and transcriptional activity under oxidative stress. This redox function is mechanistically distinct from its endonuclease activity but utilizes the same protein.

Localization of APE1 is primarily nuclear, consistent with its role in DNA repair, but it is also found in mitochondria and is expressed in most human tissues. Its essential involvement in maintaining genome integrity and regulating redox signaling makes APE1 a focus of biomedical research, particularly in cancer biology. Inhibitors targeting either its endonuclease or redox activities are being explored to enhance the effectiveness of chemotherapy and radiotherapy.