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: Amila Suraweera, Olivier J Becherel, Philip Chen, Natalie Rundle, Rick Woods, Jun Nakamura, Magtouf Gatei, Chiara Criscuolo, Alessandro Filla, Luciana Chessa, Markus Fusser, Bernd Epe, Nuri Gueven, Martin F Lavin
• Journal: The Journal of cell biology (J Cell Biol) Vol. 177 Issue 6 Pg. 969-79 (Jun 18 2007) ISSN: 0021-9525 [Print] United States
• PMID: 17562789 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Multifunctional Enzymes
• Hydrogen Peroxide
• SETX protein, human
• DNA Helicases
• RNA Helicases

Topics

• Apraxias (etiology, pathology)
• Ataxia (etiology, pathology)
• Cells, Cultured
• DNA Breaks, Double-Stranded
• DNA Damage
• DNA Helicases
• DNA Repair
• Humans
• Hydrogen Peroxide (pharmacology)
• Multifunctional Enzymes
• Oxidative Stress
• RNA Helicases (physiology)