DNA-(apurinic or apyrimidinic site) lyase 2; AP endonuclease XTH2; APEX nuclease 2; APEX nuclease-like 2; apurinic-apyrimidinic endonuclease 2; AP endonuclease 2 (APEX2, APE2, APEXL2, XTH2)

Function

• nuclear & mitochondrial post-replication base excision repair
• weak apurinic/apyrimidinic (AP) endodeoxyribonuclease in the DNA base excision repair pathway of DNA lesions induced by oxidative & alkylating agents
• initiates repair of apurinic/apyrimidinic 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 & 3'-hydroxyl ends.
• displays also double-stranded DNA 3'-5' exonuclease, 3'-phosphodiesterase activities
• robust 3'-5' exonuclease activity on 3'-recessed heteroduplex DNA & is able to remove mismatched nucleotides preferentially
• shows fairly strong 3'-phosphodiesterase activity involved in the removal of 3'-damaged termini formed in DNA by oxidative agents
• in the nucleus functions in the PCNA-dependent DNA base excision repair pathway
• required for somatic hypermutation & DNA cleavage step of class switch recombination of immunoglobulin genes
• required for proper cell cycle progression during proliferation of peripheral lymphocytes
• the C-O-P bond 3' to the apurinic or apyrimidinic site in DNA is broken by a beta-elimination reaction, leaving a 3'-terminal unsaturated sugar & a product with a terminal 5'-phosphate
• 3'-5' exonuclease activity is activated by Na+ & Mn+2
• 3'-5' exonuclease & 3'-phosphodiesterase activities are stimulated in presence of PCNA
• interacts with PCNA; interaction is triggered by reactive oxygen species & increased by misincorporation of uracil in nuclear DNA

Kinetic parameters:

• pH dependence: optimum pH is 6.0-8.0

Structure

belongs to the DNA repair enzymes AP/exoA family

Compartment

• nuclear, probably mitochondrial
• colocalizes partly with PCNA

Expression

• highly expressed in cells, adult brain, kidney
• weakly expressed in the fetal brain

More general terms

• lyase
• nuclear protein
• mitochondrial protein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=27301
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:27301
• OMIM: https://mirror.omim.org/entry/300773
• UniProt: http://www.uniprot.org/uniprot/Q9UBZ4.html