Apurinic/Apyrimidinic Endonuclease Functions in DNA Repair Mechanisms

Apurinic/apyrimidinic endonuclease 1 (APE1) is the principal enzyme responsible for recognising and cleaving abasic sites—locations in DNA where bases have been lost due to spontaneous hydrolysis or damage. Operating at the heart of the base excision repair (BER) pathway, APE1 initiates repair by incising the phosphodiester backbone 5′ to apurinic/apyrimidinic (AP) sites, thereby generating termini that can be processed by DNA polymerases and ligases. Beyond its DNA repair function, APE1 also exerts redox control over transcription factors, modulating gene expression programmes in response to oxidative stress. The duality of APE1 roles—nuclease activity and redox regulation—underpins its significance in maintaining genome stability, regulating cellular senescence and ageing, and influencing tumour biology. Dysregulation of APE1 has been implicated in chemoresistance, accelerated ageing phenotypes and defective mitochondrial DNA maintenance. Emerging evidence highlights APE1 involvement in RNA processing, mitochondrial targeting and modulation of signalling networks, underscoring the enzyme’s versatility as a potential biomarker and therapeutic target across a range of diseases.

Research from Nature Portfolio

Recent studies have elucidated a novel role for APE1 in post-transcriptional regulation. Investigations into APE1’s interactome reveal that, under genotoxic stress, it associates with components of the microRNA biogenesis machinery to influence pri-miRNA processing. This function requires APE1’s endonuclease activity and contributes to the regulation of key tumour suppressors by controlling levels of miR-221/222. The work also demonstrates that disruptions in APE1-mediated miRNA maturation can alter cell survival pathways in cancer, linking DNA repair processes directly to gene expression networks through an unsuspected RNA-based mechanism.

Apurinic/Apyrimidinic Endonuclease Functions in DNA Repair Mechanisms publication trend

The graph below shows the total number of articles in apurinic/apyrimidinic endonuclease functions in dna repair mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

Apurinic/apyrimidinic endonuclease (APE1): The enzyme that recognises and cleaves abasic sites in DNA, initiating the base excision repair pathway.

Base excision repair (BER): A cellular mechanism that corrects small, non-helix-distorting base lesions in DNA through removal of damaged bases and strand incision.

Apurinic/apyrimidinic (AP) site: A lesion in DNA where a purine or pyrimidine base is missing, creating an abasic site that must be repaired to maintain genome integrity.

Redox activity: The ability of APE1 to modulate the oxidation state of transcription factors, influencing their DNA-binding capacity and activity.

MicroRNA (miRNA): Small non-coding RNAs that regulate gene expression post-transcriptionally by targeting messenger RNAs for degradation or translational repression.

References

1. Mammalian APE1 controls miRNA processing and its interactome is linked to cancer RNA metabolism. Nature Communications (2017).
2. Small-molecule inhibition of APE1 induces apoptosis, pyroptosis, and necroptosis in non-small cell lung cancer. Cell Death & Disease (2021).
3. Identification and Characterization of Mitochondrial Targeting Sequence of Human Apurinic/Apyrimidinic Endonuclease 1*. Journal of Biological Chemistry (2010).
4. APE1 deficiency promotes cellular senescence and premature aging features. Nucleic Acids Research (2018).