APEX2 (Apurinic/Apyrimidinic Endodeoxyribonuclease 2) encodes a DNA repair enzyme that plays a critical role in the [base excision repair (BER) pathway](/mechanisms/dna-repair-pathways). APEX2 is a mitochondrial and nuclear protein that recognizes and cleaves apurinic/apyrimidinic (AP) sites - potentially lethal DNA lesions generated spontaneously or through oxidative damage. Given the high metabolic rate and oxygen consumption of [neurons](/entities/neurons), APEX2-mediated DNA repair is particularly important for neuronal survival and has been implicated in [Alzheimer's disease](/diseases/alzheimers-disease), [Parkinson's disease](/diseases/parkinsons-disease), [amyotrophic lateral sclerosis](/diseases/amyotrophic-lateral-sclerosis), and [Huntington's disease](/diseases/huntingtons).
Gene Overview
| Attribute | Value | |-----------|-------| | Symbol | APEX2 | | Full Name | Apurinic/Apyrimidinic Endodeoxyribonuclease 2 | | Chromosome | 11p13 | | NCBI Gene ID | [27351](https://www.ncbi.nlm.nih.gov/gene/27351) | | OMIM ID | [607538](https://www.omim.org/entry/607538) | | UniProt ID | [Q9GZL2](https://www.uniprot.org/uniprot/Q9GZL2) | | Ensembl ID | [ENSG00000164073](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000164073) |
Protein Structure and Function
APEX2 is a ~57 kDa protein with the following functional characteristics:
DNA binding domain - Recognizes AP sites in DNA
Endonuclease active site - Catalyzes cleavage 5' to the AP site
Iron-sulfur cluster - Contains a 4Fe-4S cluster essential for catalytic activity
Mitochondrial targeting sequence - Directs protein to mitochondria
Nuclear localization signal - Allows nuclear import
APEX2 functions in the base excision repair pathway:
Damage recognition - Identifies AP sites generated by spontaneous depurination or glycosylase action
Strand cleavage - Endonucleolytically cleaves the DNA backbone 5' to the AP site
DNA repair - Works with DNA polymerase and ligase to complete repair
Mitochondrial DNA repair - Particularly important for mtDNA maintenance
Brain Expression and Localization
APEX2 is expressed in various brain regions with both nuclear and mitochondrial localization:
Neurons - High expression in cortical and hippocampal neurons
[Astrocytes](/entities/astrocytes) - Moderate expression supporting DNA repair capacity
Oligodendrocytes - Expression for myelin DNA maintenance
[Microglia](/cell-types/microglia-neuroinflammation) - DNA repair in immune cells
The mitochondrial localization is particularly important in neurons due to:
High mitochondrial energy demands
[Reactive oxygen species](/entities/reactive-oxygen-species) (ROS) production
Limited mitochondrial DNA repair capacity compared to nuclear DNA
Disease Associations
Alzheimer's Disease
APEX2 is implicated in [Alzheimer's disease](/diseases/alzheimers-disease) through:
Oxidative DNA damage - Increased AP sites in AD brain
BER pathway dysfunction - Impaired APEX2 activity in AD