InterPro domain: IPR026963

Aprataxin is a DNA-binding protein involved in single-strand and double-strand DNA break repair, and base excision repair [ 1 , 2 , 3 ]. In yeast the aprataxin orthologue is known as Hnt3 (Hit family protein 3) [ 4 ]. Aprataxin is a member of the histidine triad (HIT) superfamily of nucleotide hydrolases and transferases, named for their characteristic HxHxHxx catalytic motif, where x is a hydrophobic amino acid [ 5 ]. It also contains an N-terminal forkhead associated (FHA) domain, which is thought to mediate interactions with the ligase cofactors XRCC1 and XRCC4, and a C-terminal zinc finger domain implicated in DNA binding [ 6 , 7 ].

Aprataxin repairs adenylated RNA-DNA junctions [ 8 ]. It resolves abortive DNA ligation intermediates formed either at base excision sites, or when DNA ligases attempt to repair non-ligatable breaks induced by reactive oxygen species. It catalyses the release of adenylate groups covalently linked to 5'-phosphate termini, resulting in the production of 5'-phosphate termini that can be efficiently rejoined [ 9 ]. Mutations in the aprataxin gene cause the neurological disorder ataxia oculomotor apraxia-1 (AOA1).

This entry also includes the Aprataxin-like protein BHLH140.

1. Aprataxin, a novel protein that protects against genotoxic stress. Hum. Mol. Genet. 13, 1081-93
2. Aprataxin forms a discrete branch in the HIT (histidine triad) superfamily of proteins with both DNA/RNA binding and nucleotide hydrolase activities. J. Biol. Chem. 281, 13939-48
3. Actions of aprataxin in multiple DNA repair pathways. J. Biol. Chem. 282, 9469-74
4. Crystal structures of aprataxin ortholog Hnt3 reveal the mechanism for reversal of 5'-adenylated DNA. Nat. Struct. Mol. Biol. 18, 1297-9
5. Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene. Nat. Genet. 29, 184-8
6. The FHA domain of aprataxin interacts with the C-terminal region of XRCC1. Biochem. Biophys. Res. Commun. 325, 1279-85
7. The ataxia-oculomotor apraxia 1 gene product has a role distinct from ATM and interacts with the DNA strand break repair proteins XRCC1 and XRCC4. DNA Repair (Amst.) 3, 1493-502
8. Aprataxin resolves adenylated RNA-DNA junctions to maintain genome integrity. Nature 506, 111-5
9. The neurodegenerative disease protein aprataxin resolves abortive DNA ligation intermediates. Nature 443, 713-6