Reaction: (1) adenosine-5'-diphospho-5'-[DNA] + H2O = AMP + phospho-5'-[DNA]
(2) adenosine-5'-diphospho-5'-(ribonucleotide)-[DNA] + H2O = AMP + 5'-phospho-(ribonucleotide)-[DNA]
Other name(s): aprataxin; 5'-App5'-DNA adenylate hydrolase; APTX (gene name); HNT3 (gene name)
Systematic name: adenosine-5'-diphospho-5'-[DNA] hydrolase (adenosine 5'-phosphate-forming)
Comments: Aprataxin is a DNA-binding protein involved in different types of DNA break repair. The enzyme acts (among other activities) on abortive DNA ligation intermediates that contain an adenylate covalently linked to the 5'-phosphate DNA terminus. It also acts when the adenylate is covalently linked to the 5'-phosphate of a ribonucleotide linked to a DNA strand, which is the result of abortive ligase activty on products of EC 3.1.26.4, ribonuclease H, an enzyme that cleaves RNA-DNA hybrids on the 5' side of the ribonucleotide found in the 5'-RNA-DNA-3' junction. Aprataxin binds the adenylate group to a histidine residue within the active site, followed by its hydrolysis from the nucleic acid and eventual release, leaving a 5'-phosphate terminus that can be efficiently rejoined. The enzyme also possesses the activities of EC 3.6.1.70, guanosine-5'-diphospho-5'-[DNA] diphosphatase, and EC 3.6.1.72, DNA-3'-diphospho-5'-guanosine diphosphatase.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Ahel, I., Rass, U., El-Khamisy, S.F., Katyal, S., Clements, P.M., McKinnon, P.J., Caldecott, K.W. and West, S.C. The neurodegenerative disease protein aprataxin resolves abortive DNA ligation intermediates. Nature 443 (2006) 713-716. [PMID: 16964241]
2. Tumbale, P., Williams, J.S., Schellenberg, M.J., Kunkel, T.A. and Williams, R.S. Aprataxin resolves adenylated RNA-DNA junctions to maintain genome integrity. Nature 506 (2014) 111-115. [PMID: 24362567]