<div is a human gene whose product aPE1 (Apurinic/Apyrimidinic Endonuclease 1)** is a essential DNA repair enzyme that plays a critical role in the base excision repair (BER) pathway. It recognizes and cleaves apurinic/apyrimidinic (AP) sites in DNA that arise spontaneously or from oxidative damage. APE1 also has redox function (Ref-1) regulating transcription factor activity including AP-1, NF-κB, p53, and HIF-1α[1]. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
| Symbol | APE1 |
|---|---|
| Full Name | Apurinic/Apyrimidinic Endonuclease 1 |
| Chromosomal Location | 14q11.2 |
| NCBI Gene ID | https://www.ncbi.nlm.nih.gov/gene/328 328 |
| OMIM | https://www.omim.org/entry/107323 107323 |
| Ensembl ID | ENSG00000100823 |
| UniProt | https://www.uniprot.org/uniprot/P27695 P27695 |
| Associated Diseases | [Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), [ALS](/diseases/amyotrophic-lateral-sclerosis) |
APE1 (Apurinic/Apyrimidinic Endonuclease 1) is a essential DNA repair enzyme that plays a critical role in the base excision repair (BER) pathway. It recognizes and cleaves apurinic/apyrimidinic (AP) sites in DNA that arise spontaneously or from oxidative damage. APE1 also has redox function (Ref-1) regulating transcription factor activity including AP-1, NF-κB, p53, and HIF-1α[1:1].
APE1 is the central enzyme in the base excision repair (BER) pathway, which handles small, non-bulky DNA lesions caused by oxidative damage, alkylation, and deamination[2]:
APE1's endonuclease activity is essential—without it, AP sites accumulate, leading to strand breaks, genomic instability, and cell death.
Beyond DNA repair, APE1's N-terminal domain possesses redox activity, functioning as a "redox factor-1" (Ref-1)[3]. This activity:
The dual functionality makes APE1 unique: a "two-faced" protein balancing genomic stability and transcriptional regulation.
APE1 localizes to both nucleus and mitochondria, where it performs essential mitochondrial DNA (mtDNA) repair. Dopaminergic neurons have high metabolic demands and are particularly vulnerable to mtDNA damage. APE1 deficiency in mitochondria contributes to:
APE1 dysfunction is central to multiple neurodegenerative diseases due to its essential role in DNA repair and redox regulation.
APE1 deficiency contributes to accumulation of oxidative DNA damage in neurons[5]. Key mechanisms include:
APE1 polymorphisms associated with PD risk. Important for repair of mitochondrial DNA damage in dopaminergic neurons:
Oxidative DNA damage accumulation in motor neurons:
APE1 activity declines with age, contributing to genomic instability and neurodegeneration:
Broad expression throughout the brain, with high levels in neurons. Subcellular localization: nucleus and mitochondria. Expression is upregulated in response to oxidative stress.
APE1 is a 36 kDa protein with two functional domains:
The catalytic site uses a metal-dependent mechanism (Mg²⁺) to cleave the phosphodiester bond 5' to AP sites. The active site His309 acts as a general acid/base, while Asp283 coordinates the metal ion.
APE1 represents a promising therapeutic target for neurodegenerative diseases[7]:
Tell et al. The多元化 functions of APE1/Ref-1 (2009). 2009. ↩︎ ↩︎
Caldecott KW. DNA single-strand break repair and human disease (2020). 2020. ↩︎
Demple B. Rediscovering the function of APE1/Ref-1 in the nucleus (2019). 2019. ↩︎
Fung et al. APE1/Ref-1 in neurodegeneration (2021). 2021. ↩︎
Coppedè et al. DNA repair deficiency in neurodegeneration (2011). 2011. ↩︎
Thakur et al. APE1 and Alzheimer's disease (2019). 2019. ↩︎
Shah F, et al. Exploiting the Ref-1 redox activity for neuroprotection (2015). 2015. ↩︎