Understanding APE1 cellular functions by the structural preference of exonuclease activities

Abstract

Graphical abstract

Epidemiological Evidence for Associations Between Genetic Variants and Osteosarcoma Susceptibility: A Meta-Analysis

“…The apurinic/apyrimidinic endodeoxyribonuclease 1 ( APE1 ) gene may be involved in the specific activation of DNA repair and numerous malignancies ( 26 , 27 ). This study presented strong evidence of the association between a polymorphism (rs1760944) and lower OS risk.…”

Exonucleases: Degrading DNA to Deal with Genome Damage, Cell Death, Inflammation and Cancer

“…Distinct exonucleases, such as APE1 [ 10 ], EXO1 [ 11 ], FAN1 [ 12 ], and FEN1 [ 13 ], are important components of several DNA repair pathways, including base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), non-homologous end joining (NHEJ), homologous recombination (HR), single-strand break repair (SSBR), post-replication repair (PRR) or DNA damage tolerance (DDT), interstrand cross-link repair (ICL), stalled replication fork and hairpin structure repair, as well as polymerase proofreading, as detailed below. Their ability to cleave DNA allows the elimination of damaged or mismatched nucleotides, which facilitates subsequent insertion of the correct base [ 14 ].…”

“…Similarly, the keratinocyte-specific TREX2 exonuclease promotes the passage of UVB-irradiated keratinocytes to late non-reversible apoptotic stages [ 22 ]. Other exonucleases participate in the degradation of DNA upon apoptosis activation, such as ARTEMIS [ 23 ], FEN1 [ 13 ] and APE1 [ 10 ].…”

“…Apurinic/apyrimidinic endonuclease 1 (APE1), APEX1 or reduction-oxidation factor (Ref1), is a multifunctional enzyme, its main function being to incise the phosphodiester bond immediately 5′ to apurinic/apyrimidinic (AP) sites to generate single-strand breaks (SSBs). However, this protein also possesses 3′–5′ exonuclease activity [ 10 ]. It is involved in maintaining genome stability, participating in several DNA repair pathways such as tri-nucleotide repair (TNR) by the removal of hairpin structures and BER, digestion of matched and mismatched 3′ ends of duplex DNA structures, and the recognition of SSBs to induce their repair, and in apoptosis by exonucleolytic digestion of chromosomal fragments.…”

“…It is involved in maintaining genome stability, participating in several DNA repair pathways such as tri-nucleotide repair (TNR) by the removal of hairpin structures and BER, digestion of matched and mismatched 3′ ends of duplex DNA structures, and the recognition of SSBs to induce their repair, and in apoptosis by exonucleolytic digestion of chromosomal fragments. It also prevents the formation of double-strand breaks (DSBs) during the repair of bi-stranded clustered DNA damage by nucleotide incision repair (NIR), which repairs oxidative damage in nucleotides, and interacts with POLB [ 10 ] to carry out proofreading.…”