A subgroup of spinocerebellar ataxias defective in DNA damage responses

Gueven, N., Chen, P., Nakamura, J., Becherel, O.J., Kijas, A.W., Grattan-Smith, P. and Lavin, M.F. (2007) A subgroup of spinocerebellar ataxias defective in DNA damage responses. Neuroscience, 145 4: 1418-1425. doi:10.1016/j.neuroscience.2006.12.010

Author Gueven, N.
Chen, P.
Nakamura, J.
Becherel, O.J.
Kijas, A.W.
Grattan-Smith, P.
Lavin, M.F.
Title A subgroup of spinocerebellar ataxias defective in DNA damage responses
Journal name Neuroscience   Check publisher's open access policy
ISSN 0306-4522
Publication date 2007-04-14
Sub-type Article (original research)
DOI 10.1016/j.neuroscience.2006.12.010
Volume 145
Issue 4
Start page 1418
End page 1425
Total pages 8
Place of publication Oxford, u.k.
Publisher Pergamon-elsevier Science Ltd
Language eng
Subject C1
320307 Medical Biochemistry - Other
730100 Clinical (Organs, Diseases and Abnormal Conditions)
Abstract A subgroup of human autosomal recessive ataxias is also characterized by disturbances of eye movement or oculomotor apraxia. These include ataxia telangiectasia (AT); ataxia telangiectasia like disorder (ATLD); ataxia oculomotor apraxia type 1 (AOA1) and ataxia oculomotor apraxia type 2 (AOA2). What appears to be emerging is that all of these have in common some form of defect in DNA damage response which could account for the neurodegenerative changes seen in these disorders. We describe here sensitivity to DNA damaging agents in AOA1 and evidence that these cells have a defect in single strand break repair. Comparison is made with what appears to be a novel form of AOA (AOA3) which also shows sensitivity to agents that lead to single strand breaks in DNA as well as a reduced capacity to repair these breaks. AOA3 cells are defective in the DNA damage-induced p53 response. This defect can be overcome by incubation with the mdm2 antagonists, nutlins, but combined treatment with nutlins and DNA damage does not enhance the response. We also show that AOA3 cells are deficient in p73 activation after DNA damage. These data provide further evidence that different forms of AOA have in common a reduced capacity to cope with damage to DNA, which may account for the neurodegeneration observed in these syndromes. (C) 2006 IBRO. Published by Elsevier Ltd. All rights reserved.
Keyword Neurosciences
spinocerebellar ataxia
DNA repair
Strand-break Repair
Protein Aprataxin
P53 Family
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2008 Higher Education Research Data Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 38 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 41 times in Scopus Article | Citations
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Created: Tue, 19 Feb 2008, 03:06:06 EST