Aprataxin, a novel protein that protects against genotoxic stress

Gueven, Nuri, Becherel, Olivier J., Kijas, Amanda W., Chen, Philip, Howe, Orla, Rudolph, Jeanette H., Gatti, Richard, Date, Hidetoshi, Onodera, Osamu, Taucher-Scholz, Gisela and Lavin, Martin F. (2004) Aprataxin, a novel protein that protects against genotoxic stress. Human Molecular Genetics, 13 10: 1081-1093. doi:10.1093/hmg/ddh122

Author Gueven, Nuri
Becherel, Olivier J.
Kijas, Amanda W.
Chen, Philip
Howe, Orla
Rudolph, Jeanette H.
Gatti, Richard
Date, Hidetoshi
Onodera, Osamu
Taucher-Scholz, Gisela
Lavin, Martin F.
Title Aprataxin, a novel protein that protects against genotoxic stress
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 0964-6906
Publication date 2004-05-15
Year available 2004
Sub-type Article (original research)
DOI 10.1093/hmg/ddh122
Open Access Status Not Open Access
Volume 13
Issue 10
Start page 1081
End page 1093
Total pages 13
Editor H. Willard
K. Davies
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Collection year 2004
Language eng
Abstract 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.
Keyword Biochemistry & molecular biology
Genetics &heredity
Strand break repair
Base excision-repair
Ocular motor apraxia
Early-onset Ataxia
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2005 Higher Education Research Data Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 108 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 116 times in Scopus Article | Citations
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Created: Wed, 15 Aug 2007, 03:24:09 EST