title: Senataxin, defective in ataxia oculomotor apraxia type 2, is involved in the defense against oxidative DNA damage.
abstract: A defective response to DNA damage is observed in several human autosomal recessive ataxias with oculomotor apraxia, including ataxia-telangiectasia. We report that senataxin, defective in ataxia oculomotor apraxia (AOA) type 2, is a nuclear protein involved in the DNA damage response. AOA2 cells are sensitive to H2O2, camptothecin, and mitomycin C, but not to ionizing radiation, and sensitivity was rescued with full-length SETX cDNA. AOA2 cells exhibited constitutive oxidative DNA damage and enhanced chromosomal instability in response to H2O2. Rejoining of H2O2-induced DNA double-strand breaks (DSBs) was significantly reduced in AOA2 cells compared to controls, and there was no evidence for a defect in DNA single-strand break repair. This defect in DSB repair was corrected by full-length SETX cDNA. These results provide evidence that an additional member of the autosomal recessive AOA is also characterized by a defective response to DNA damage, which may contribute to the neurodegeneration seen in this syndrome.
authors.affiliation: Radiation Biology and Oncology Laboratory, Queensland Institute of Medical Research, Brisbane, QLD 4029, Australia.
authors.forename: Amila
authors.initials: A
authors.lastname: Suraweera
authors.forename: Olivier J
authors.initials: OJ
authors.lastname: Becherel
authors.forename: Philip
authors.initials: P
authors.lastname: Chen
authors.forename: Natalie
authors.initials: N
authors.lastname: Rundle
authors.forename: Rick
authors.initials: R
authors.lastname: Woods
authors.forename: Jun
authors.initials: J
authors.lastname: Nakamura
authors.forename: Magtouf
authors.initials: M
authors.lastname: Gatei
authors.forename: Chiara
authors.initials: C
authors.lastname: Criscuolo
authors.forename: Alessandro
authors.initials: A
authors.lastname: Filla
authors.forename: Luciana
authors.initials: L
authors.lastname: Chessa
authors.forename: Markus
authors.initials: M
authors.lastname: Fusser
authors.forename: Bernd
authors.initials: B
authors.lastname: Epe
authors.forename: Nuri
authors.initials: N
authors.lastname: Gueven
authors.forename: Martin F
authors.initials: MF
authors.lastname: Lavin
mesh_terms: D001072:Apraxias / Q000209:etiology / Q000473:pathology; D001259:Ataxia / Q000209:etiology / Q000473:pathology; D002478:Cells, Cultured; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004265:DNA Helicases; D004260:DNA Repair; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D064251:Multifunctional Enzymes; D018384:Oxidative Stress; D020365:RNA Helicases / Q000502:physiology*
chemical_list: D064251:Multifunctional Enzymes; D006861:Hydrogen Peroxide; C484368:SETX protein, human; D004265:DNA Helicases; D020365:RNA Helicases