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Senataxin, defective in ataxia oculomotor apraxia type 2, is involved in the defense against oxidative DNA damage
Citation
Suraweera, A and Becherel, OJ and Chen, P and Rundle, N and Woods, R and Nakamura, J and Gatei, M and Criscuolo, C and Filla, A and Chessa, L and Fusser, M and Epe, B and Guven, N and Lavin, MF, Senataxin, defective in ataxia oculomotor apraxia type 2, is involved in the defense against oxidative DNA damage, The Journal of Cell Biology, 177, (6) pp. 969-979. ISSN 1540-8140 (2007) [Refereed Article]
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Copyright Statement
Copyright 2007 Rockefeller University Press
DOI: doi:10.1083/jcb.200701042
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.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | senataxin, ataxia oculomotor apraxia 2, DNA damage response |
| Research Division: | Medical and Health Sciences |
| Research Group: | Medical Biochemistry and Metabolomics |
| Research Field: | Medical Biochemistry: Proteins and Peptides (incl. Medical Proteomics) |
| Objective Division: | Expanding Knowledge |
| Objective Group: | Expanding Knowledge |
| Objective Field: | Expanding Knowledge in the Medical and Health Sciences |
| Author: | Guven, N (Dr Nuri Guven) |
| ID Code: | 79278 |
| Year Published: | 2007 |
| Web of Science® Times Cited: | 112 |
| Deposited By: | Pharmacy |
| Deposited On: | 2012-08-29 |
| Last Modified: | 2013-03-18 |
| Downloads: | 0 |
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