title: Mutant AP endonuclease in patients with amyotrophic lateral sclerosis.
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.
authors.affiliation: Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30335-3801, USA.
authors.forename: Z L
authors.initials: ZL
authors.lastname: Olkowski
mesh_terms: D000595:Amino Acid Sequence; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000235:genetics*; D019757:Carbon-Oxygen Lyases / Q000235:genetics* / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D043223:Deoxyribonuclease IV (Phage T4-Induced); D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology*; D010084:Oxidation-Reduction; D016133:Polymerase Chain Reaction
chemical_list: D043223:Deoxyribonuclease IV (Phage T4-Induced); D019757:Carbon-Oxygen Lyases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase