Aprataxin Forms a Discrete Branch in the HIT (Histidine Triad) Superfamily of Proteins with Both DNA/RNA Binding and Nucleotide Hydrolase Activities

Kijas, Amanda, Harris, Janelle, Harris, Jonathan, & Lavin, Martin (2006) Aprataxin Forms a Discrete Branch in the HIT (Histidine Triad) Superfamily of Proteins with Both DNA/RNA Binding and Nucleotide Hydrolase Activities. Journal of Biological Chemistry, 281(20), pp. 13939-13948.

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Abstract

Ataxia with oculomotor apraxia type 1 (AOA1) is an early onset autosomal recessive spinocerebellar ataxia with a defect in the protein Aprataxin, implicated in the response of cells to DNA damage. We describe here the expression of a recombinant form of Aprataxin and show that it has dual DNA binding and nucleotide hydrolase activities. This protein binds to double-stranded DNA with high affinity but is also capable of binding double-stranded RNA and single-strand DNA, with increased affinity for hairpin structures. No increased binding was observed with a variety of DNA structures mimicking intermediates in DNA repair. The DNA binding observed here was not dependent on zinc, and the addition of exogenous zinc abolished DNA binding. We also demonstrate that Aprataxin hydrolyzes with similar efficiency the model histidine triad nucleotide-binding protein substrate, AMPNH2, and the Fragile histidine triad protein substrate, Ap4A. These activities were significantly reduced in the presence of duplex DNA and to a lesser extent in the presence of single-strand DNA, and removal of the N-terminal Forkhead associated domain did not alter activity. Finally, comparison of sequence relationships between the histidine triad superfamily members shows that Aprataxin forms a distinct branch in this superfamily. In addition to its capacity for nucleotide binding and hydrolysis, the observation that it also binds DNA and RNA adds a new dimension to this superfamily of proteins and provides further support for a role for Aprataxin in the cellular response to DNA damage.

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54 citations in Scopus
50 citations in Web of Science®
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ID Code: 44636
Item Type: Journal Article
Refereed: Yes
Additional Information: This research was originally published in the Journal of Biological Chemistry. Amanda W. Kijas, Janelle L. Harris, Jonathan M. Harris and Martin F. Lavin. Aprataxin Forms a Discrete Branch in the HIT (Histidine Triad) Superfamily of Proteins with Both DNA/RNA Binding and Nucleotide Hydrolase Activities. Journal of Biological Chemistry. 2006; 281:13939-13948. © the American Society for Biochemistry and Molecular Biology.
DOI: 10.1074/jbc.M507946200
ISSN: 0021-9258
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100)
Australian and New Zealand Standard Research Classification > ENGINEERING (090000) > CHEMICAL ENGINEERING (090400)
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 24 Aug 2011 22:13
Last Modified: 14 May 2017 23:42

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