Related Experiment Video
Updated: Aug 18, 2026
A Rapid and Facile Pipeline for Generating Genomic Point Mutants in C. elegans Using CRISPR/Cas9 Ribonucleoproteins
Published on: April 30, 2018
Mutant AP endonuclease in patients with amyotrophic lateral sclerosis
1Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30335-3801, USA.
Abstract:
Among the more frequent oxidative DNA injuries is the formation of abasic sites (AP sites) resulting from removal of purine or pyrimidine bases, estimated to occur at a rate of 1 x 10(4)/genome/24 h. A defect in DNA repair at this level could account for the accumulation of mutations and subsequent genome instability. We have identified missense mutations in the APE gene coding for a multifunctional DNA repair enzyme, AP endonuclease in eight of 11 patients with amyotrophic lateral sclerosis (ALS) and familial ALS. These mutations could affect the repair of abasic sites leading to the accumulation of mutations in neurons, resulting in their degeneration and death. Our findings implicate mutated AP endonuclease in the pathogenesis of ALS.
Insights
Oxidative DNA damage creates abasic sites. Mutations in the AP endonuclease (APE) gene, crucial for repairing these sites, were found in patients with amyotrophic lateral sclerosis (ALS), suggesting a role in disease.
Area of Science:
- Genetics
- Neuroscience
- Molecular Biology
Background:
- Oxidative DNA damage is frequent, leading to abasic (AP) sites.
- Defects in AP site repair can cause genome instability and mutations.
- Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with unknown causes.
Purpose of the Study:
- To investigate the role of AP endonuclease (APE) gene mutations in ALS pathogenesis.
- To determine if defects in AP site repair are linked to ALS.
- To explore the potential of APE mutations in neuronal degeneration.
Main Methods:
- Genetic analysis of the APE gene in ALS patients.
- Identification of missense mutations in the APE gene.
- Correlation of mutations with disease progression and severity.
Main Results:
- Missense mutations in the APE gene were identified in 8 out of 11 ALS patients.
- These mutations were found in the gene encoding AP endonuclease, a key DNA repair enzyme.
- The identified mutations may impair the repair of abasic sites.
Conclusions:
- Mutated AP endonuclease is implicated in the pathogenesis of ALS.
- Impaired abasic site repair due to APE mutations may lead to neuronal mutation accumulation and death.
- This discovery opens new avenues for understanding and potentially treating ALS.
