Multifunctional protein that plays a central role in the cellular response to oxidative stress. The two major activities of APEX1 are DNA repair and redox regulation of transcriptional factors. Functions as a apurinic/apyrimidinic (AP) endodeoxyribonuclease in the DNA base excision repair (BER) pathway of DNA lesions induced by oxidative and alkylating agents. Initiates repair of AP sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage, generating a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl ends. Does also incise at AP sites in the DNA strand of DNA/RNA hybrids, single-stranded DNA regions of R-loop structures, and single-stranded RNA molecules. Has a 3'-5' exoribonuclease activity on mismatched deoxyribonucleotides at the 3' termini of nicked or gapped DNA molecules during short-patch BER. Possesses a DNA 3' phosphodiesterase activity capable of removing lesions (such as phosphoglycolate) blocking the 3' side of DNA strand breaks. May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation. Acts as a loading factor for POLB onto non-incised AP sites in DNA and stimulates the 5'-terminal deoxyribose 5'-phosphate (dRp) excision activity of POLB. Plays a role in the protection from granzymes-mediated cellular repair leading to cell death. Also involved in the DNA cleavage step of class switch recombination (CSR). On the other hand, APEX1 also exerts reversible nuclear redox activity to regulate DNA binding affinity and transcriptional activity of transcriptional factors by controlling the redox status of their DNA-binding domain, such as the FOS/JUN AP-1 complex after exposure to IR. Involved in calcium-dependent down-regulation of parathyroid hormone (PTH) expression by binding to negative calcium response elements (nCaREs). Together with HNRNPL or the dimer XRCC5/XRCC6, associates with nCaRE, acting as an activator of transcriptional repression. Stimulates the YBX1-mediated MDR1 promoter activity, when acetylated at Lys-6 and Lys-7, leading to drug resistance. Acts also as an endoribonuclease involved in the control of single-stranded RNA metabolism. Plays a role in regulating MYC mRNA turnover by preferentially cleaving in between UA and CA dinucleotides of the MYC coding region determinant (CRD). In association with NMD1, plays a role in the rRNA quality control process during cell cycle progression. Associates, together with YBX1, on the MDR1 promoter. Together with NPM1, associates with rRNA. Binds DNA and RNA. Belongs to the DNA repair enzymes AP/ExoA family. Note: This description may include information from UniProtKB.
Protein type: DNA repair, damage; DNA-binding; Deoxyribonuclease; EC 220.127.116.11; Endoplasmic reticulum; Hydrolase; Lyase; Nuclear receptor co-regulator; Nucleolus; Transcription, coactivator/corepressor
Molecular Function: 3'-5' exonuclease activity; 3'-5'-exodeoxyribonuclease activity; chromatin DNA binding; class II DNA-(apurinic or apyrimidinic site) endonuclease activity; damaged DNA binding; DNA binding; DNA-(abasic site) binding; DNA-(apurinic or apyrimidinic site) endonuclease activity; double-stranded DNA 3'-5' exodeoxyribonuclease activity; double-stranded DNA exodeoxyribonuclease activity; double-stranded telomeric DNA binding; endodeoxyribonuclease activity; endonuclease activity; metal ion binding; NF-kappaB binding; oxidoreductase activity; phosphodiesterase activity, acting on 3'-phosphoglycolate-terminated DNA strands; phosphodiesterase I activity; phosphoric diester hydrolase activity; protein binding; protein-containing complex binding; RNA-DNA hybrid ribonuclease activity; site-specific endodeoxyribonuclease activity, specific for altered base; transcription coactivator activity; transcription corepressor activity; uracil DNA N-glycosylase activity
Biological Process: aging; base-excision repair; base-excision repair, gap-filling; cell redox homeostasis; cellular response to cAMP; cellular response to hydrogen peroxide; cellular response to peptide hormone stimulus; DNA catabolic process, endonucleolytic; DNA demethylation; DNA recombination; DNA repair; negative regulation of DNA-templated transcription; negative regulation of smooth muscle cell migration; positive regulation of G1/S transition of mitotic cell cycle; positive regulation of transcription by RNA polymerase II; regulation of apoptotic process; regulation of mRNA stability; response to xenobiotic stimulus; RNA phosphodiester bond hydrolysis, endonucleolytic; telomere maintenance; telomere maintenance via base-excision repair