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Aprataxin, a novel protein that protects against genotoxic stress


Gueven, N and Becherel, OJ and Kijas, AW and Chen, P and Howe, O and Rudolph, JH and Gatti, R and Date, H and Onodera, O and Taucher-Scholz, G and Lavin, MF, Aprataxin, a novel protein that protects against genotoxic stress, Human Molecular Genetics, 13, (10) pp. 1081-1093. ISSN 0964-6906 (2004) [Refereed Article]

Copyright Statement

Copyright 2004 Oxford University Press

DOI: doi:10.1093/hmg/ddh122


Ataxia-oculomotor apraxia (AOA1) is a neurological disorder with symptoms that overlap those of ataxia-telangiectasia, a syndrome characterized by abnormal responses to double-strand DNA breaks and genome instability. The gene mutated in AOA1, APTX, is predicted to code for a protein called aprataxin that contains domains of homology with proteins involved in DNA damage signalling and repair. We demonstrate that aprataxin is a nuclear protein, present in both the nucleoplasm and the nucleolus. Mutations in the APTX gene destabilize the aprataxin protein, and fusion constructs of enhanced green fluorescent protein and aprataxin, representing deletions of putative functional domains, generate highly unstable products. Cells from AOA1 patients are characterized by enhanced sensitivity to agents that cause single-strand breaks in DNA but there is no evidence for a gross defect in single-strand break repair. Sensitivity to hydrogen peroxide and the resulting genome instability are corrected by transfection with full-length aprataxin cDNA. We also demonstrate that aprataxin interacts with the repair proteins XRCC1, PARP-1 and p53 and that it co-localizes with XRCC1 along charged particle tracks on chromatin. These results demonstrate that aprataxin influences the cellular response to genotoxic stress very likely by its capacity to interact with a number of proteins involved in DNA repair. Oxford University Press 2004; all rights reserved.

Item Details

Item Type:Refereed Article
Keywords:aprataxin, ataxia oculomotor aplaxia, DNA damage repair
Research Division:Biological Sciences
Research Group:Biochemistry and cell biology
Research Field:Biochemistry and cell biology not elsewhere classified
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in the biological sciences
UTAS Author:Gueven, N (Dr Nuri Guven)
ID Code:79317
Year Published:2004
Web of Science® Times Cited:132
Deposited By:Pharmacy
Deposited On:2012-08-31
Last Modified:2014-11-05

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