Apurinic/Apyrimidinic Endonuclease 1 (APEX1)

APE; APE1; APEN; APEX; APX; HAP1; REF1; Multifunctional DNA Repair Enzyme; APEX Nuclease 1; Redox factor-1; DNA-(apurinic or apyrimidinic site) lyase

SPN	N719
HGNC	587
MGI	88042
RGD	2126
UniProt	P27695

DNA-(apurinic or apyrimidinic site) lyase is an enzyme encoded by the APEX1 gene. Apurinic/apyrimidinic (AP) sites (also called "abasic sites") occur frequently in DNA molecules by spontaneous hydrolysis, by DNA damaging agents or by DNA glycosylases that remove specific abnormal bases. AP sites are pre-mutagenic lesions that can prevent normal DNA replication. All cells, from simple prokaryotes to humans, have evolved systems to identify and repair such sites. Class II AP endonucleases cleave the phosphodiester backbone 5' to the AP site, thereby initiating a process known as base excision repair (BER). The APEX gene (alternatively named APE1, HAP1, APEN) encodes the major AP endonuclease in human cells. Splice variants have been found for this gene; all encode the same protein.

Reference

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Nucleic Acids Res. 19:5519-5523(1991) [PubMed] [Europe PMC] [Abstract]

"Cloning and expression of APE, the cDNA encoding the major human apurinic endonuclease: definition of a family of DNA repair enzymes."
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"cDNA cloning, sequencing, expression and possible domain structure of human APEX nuclease homologous to Escherichia coli exonuclease III."
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Nucleic Acids Res. 20:370-370(1992) [PubMed] [Europe PMC] [Abstract]

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Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]

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"The interaction between Ku antigen and REF1 protein mediates negative gene regulation by extracellular calcium."
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"Asparagine 212 is essential for abasic site recognition by the human DNA repair endonuclease HAP1."
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"AP-1 transcriptional activity is regulated by a direct association between thioredoxin and Ref-1."
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"Interaction of human apurinic endonuclease and DNA polymerase beta in the base excision repair pathway."
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"Rapid dissociation of human apurinic endonuclease (Ape1) from incised DNA induced by magnesium."
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"Activation of apurinic/apyrimidinic endonuclease in human cells by reactive oxygen species and its correlation with their adaptive response to genotoxicity of free radicals."
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"Phosphorylation of the DNA repair protein APE/REF-1 by CKII affects redox regulation of AP-1."
Oncogene 18:1033-1040(1999) [PubMed] [Europe PMC] [Abstract]

"Thioredoxin nuclear translocation and interaction with redox factor-1 activates the activator protein-1 transcription factor in response to ionizing radiation."
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"Activation of APE/Ref-1 redox activity is mediated by reactive oxygen species and PKC phosphorylation."
Nucleic Acids Res. 29:3116-3122(2001) [PubMed] [Europe PMC] [Abstract]

"HMG2 interacts with the nucleosome assembly protein SET and is a target of the cytotoxic T-lymphocyte protease granzyme A."
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Nature 415:655-659(2002) [PubMed] [Europe PMC] [Abstract]

"Human AP-endonuclease 1 and hnRNP-L interact with a nCaRE-like repressor element in the AP-endonuclease 1 promoter."
Nucleic Acids Res. 30:823-829(2002) [PubMed] [Europe PMC] [Abstract]

"Role of acetylated human AP-endonuclease (APE1/Ref-1) in regulation of the parathyroid hormone gene."
EMBO J. 22:6299-6309(2003) [PubMed] [Europe PMC] [Abstract]

"Novel role of tyrosine in catalysis by human AP endonuclease 1."
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"Analysis of nuclear transport signals in the human apurinic/apyrimidinic endonuclease (APE1/Ref1)."
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"Identification and characterization of mitochondrial abasic (AP)-endonuclease in mammalian cells."
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"Nitric oxide controls nuclear export of APE1/Ref-1 through S-nitrosation of cysteines 93 and 310."
Nucleic Acids Res. 35:2522-2532(2007) [PubMed] [Europe PMC] [Abstract]

"Characterization of abasic endonuclease activity of human Ape1 on alternative substrates, as well as effects of ATP and sequence context on AP site incision."
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"Regulatory role of human AP-endonuclease (APE1/Ref-1) in YB-1-mediated activation of the multidrug resistance gene MDR1."
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"Enzymatic mechanism of human apurinic/apyrimidinic endonuclease against a THF AP site model substrate."
Biochemistry 48:19-26(2009) [PubMed] [Europe PMC] [Abstract]

"APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the rRNA quality control process."
Mol. Cell. Biol. 29:1834-1854(2009) [PubMed] [Europe PMC] [Abstract]

"Identification of apurinic/apyrimidinic endonuclease 1 (APE1) as the endoribonuclease that cleaves c-myc mRNA."
Nucleic Acids Res. 37:3946-3958(2009) [PubMed] [Europe PMC] [Abstract]

"Ubiquitination of mammalian AP endonuclease (APE1) regulated by the p53-MDM2 signaling pathway."
Oncogene 28:1616-1625(2009) [PubMed] [Europe PMC] [Abstract]

"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]

"Identification and characterization of mitochondrial targeting sequence of human apurinic/apyrimidinic endonuclease 1."
J. Biol. Chem. 285:14871-14881(2010) [PubMed] [Europe PMC] [Abstract]

"SIRT1 deacetylates APE1 and regulates cellular base excision repair."
Nucleic Acids Res. 38:832-845(2010) [PubMed] [Europe PMC] [Abstract]

"Critical lysine residues within the overlooked N-terminal domain of human APE1 regulate its biological functions."
Nucleic Acids Res. 38:8239-8256(2010) [PubMed] [Europe PMC] [Abstract]

"Initial characterization of the human central proteome."
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]

"Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain."
Cell 145:423-434(2011) [PubMed] [Europe PMC] [Abstract]

"Characterization of the endoribonuclease active site of human apurinic/apyrimidinic endonuclease 1."
J. Mol. Biol. 411:960-971(2011) [PubMed] [Europe PMC] [Abstract]

"An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]

"The crystal structure of the human DNA repair endonuclease HAP1 suggests the recognition of extra-helical deoxyribose at DNA abasic sites."
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"DNA-bound structures and mutants reveal abasic DNA binding by APE1 and DNA repair coordination."
Nature 403:451-456(2000) [PubMed] [Europe PMC] [Abstract]

"Two divalent metal ions in the active site of a new crystal form of human apurinic/apyrimidinic endonuclease, Ape1: implications for the catalytic mechanism."
J. Mol. Biol. 307:1023-1034(2001) [PubMed] [Europe PMC] [Abstract]