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- Title
Senataxin, defective in ataxia oculomotor apraxia type 2, is involved in the defense against oxidative DNA damage.
- Authors
Suraweera, Amila; Becherel, Olivier J; Chen, Philip; Rundle, Natalie; Woods, Rick; Nakamura, Jun; Gatei, Magtouf; Criscuolo, Chiara; Filla, Alessandro; Chessa, Luciana; Fusser, Markus; Epe, Bernd; Gueven, Nuri; Lavin, Martin F
- 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.
- Publication
The Journal of cell biology, 2007, Vol 177, Issue 6, p969
- ISSN
0021-9525
- Publication type
Journal Article
- DOI
10.1083/jcb.200701042