Cloned (Comment) | Organism |
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gene HNT3 encodes the aprataxin homologue, APTX, of Saccharomyces cerevisiae, transient transfection of XRCC1 wild-type, XPK4, and Xrcc1-/- cells with GFP-tagged APTX, Hnt3 point mutations and complementation with human Aprataxin | Saccharomyces cerevisiae |
transient transfection of XRCC1 wild-type, XPK4, and Xrcc1-/- cells with GFP-tagged APTX. Expression of Myc-NLS-tagged human aprataxin from a plasmid complements HNT3 deletion in Saccharomyces cerevisiae | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
additional information | construction of hnt3DELTA single mutants and HNT3 knockout mutants, including apn1DELTA/apn2DELTA/tpp1DELTA and ntg1DELTA/ntg2DELTA/ogg1DELTA. Loss of HNT3 in rad27DELTA cells, which are deficient in long-patch base excision repair (LP-BER), results in synergistic sensitivity to H2O2 and methylmethane sulfonate. HNT3 deletion partially rescues H2O2 sensitivity in recombination deficient rad51DELTA and rad52DELTA cells. Hnt3 point mutations and complementation with human aprataxin. Phenotypes, overview | Saccharomyces cerevisiae |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
nucleus | - |
Homo sapiens | 5634 | - |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
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adenosine-5'-diphospho-5'-[DNA] + H2O | Homo sapiens | - |
AMP + phospho-5'-[DNA] | - |
? | |
additional information | Homo sapiens | APTX-mediated DNA deadenylation activity (i.e. 5'-AMP removal) is measured in extracts of cells expressing wild-type XRCC1 or the XRCC1 phosphorylation mutant, and compared with activity in APTX-deficient and APTX-complemented human cells. APTX activity is lower in extracts from Xrcc1-/- and XRCC1 phosphorylation mutant cells compared to the robust activity in extract from wild-type XRCC1 expressing cells. And APTX-mediated DNA deadenylation activity (i.e. 5'-AMP removal) is measured in cell extracts of the XRCC1 variants, and compared with activity in patient AOA1 human fibroblasts and APTX-complemented cells | ? | - |
? |
Organism | UniProt | Comment | Textmining |
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Homo sapiens | Q7Z2E3 | - |
- |
Saccharomyces cerevisiae | Q08702 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
fibroblast | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
adenosine-5'-diphospho-5'-[DNA] + H2O | - |
Homo sapiens | AMP + phospho-5'-[DNA] | - |
? | |
adenosine-5'-diphospho-5'-[DNA] + H2O | - |
Saccharomyces cerevisiae | AMP + phospho-5'-[DNA] | - |
? | |
additional information | APTX-mediated DNA deadenylation activity (i.e. 5'-AMP removal) is measured in extracts of cells expressing wild-type XRCC1 or the XRCC1 phosphorylation mutant, and compared with activity in APTX-deficient and APTX-complemented human cells. APTX activity is lower in extracts from Xrcc1-/- and XRCC1 phosphorylation mutant cells compared to the robust activity in extract from wild-type XRCC1 expressing cells. And APTX-mediated DNA deadenylation activity (i.e. 5'-AMP removal) is measured in cell extracts of the XRCC1 variants, and compared with activity in patient AOA1 human fibroblasts and APTX-complemented cells | Homo sapiens | ? | - |
? | |
additional information | APTX-mediated DNA deadenylation activity (i.e. 5'-AMP removal) is measured | Homo sapiens | ? | - |
? |
Synonyms | Comment | Organism |
---|---|---|
aprataxin | - |
Homo sapiens |
aprataxin | - |
Saccharomyces cerevisiae |
APTX | - |
Homo sapiens |
APTX | - |
Saccharomyces cerevisiae |
DNA-adenylate hydrolase | - |
Homo sapiens |
DNA-adenylate hydrolase | - |
Saccharomyces cerevisiae |
HNT3 | - |
Saccharomyces cerevisiae |
HNT3 | - |
Homo sapiens |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
additional information | interaction with phosphorylated XRCC1 is a requirement for significant APTX recruitment to cellular DNA damage and enzymatic activity in cell extracts. XRCC1 is a multi-domain protein without catalytic activity | Homo sapiens | |
additional information | interaction with phosphorylated XRCC1 is a requirement for significant APTX recruitment to cellular DNA damage and enzymatic activity in cell extracts. XRCC1 is a multi-domain protein without catalytic activity | Saccharomyces cerevisiae |
General Information | Comment | Organism |
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malfunction | ataxia oculomotor apraxia-1 (AOA1) is a recessive human neurodegenerative disorder linked to more than 20 distinct mutations in the gene encoding APTX. Although reminiscent of ataxia-telangiectasia, primary AOA1 fibroblasts exhibit only mild hypersensitivity to ionizing radiation | Homo sapiens |
malfunction | while hnt3DELTA single mutants are not sensitive to DNA damaging agents, loss of HNT3 causes synergistic sensitivity to H2O2 in backgrounds that accumulate strand breaks with blocked termini, including apn1DELTA/apn2DELTA/tpp1DELTA and ntg1DELTA/ntg2DELTA/ogg1DELTA. Loss of HNT3 in rad27DELTA cells, which are deficient in long-patch base excision repair (LP-BER), results in synergistic sensitivity to H2O2 and methylmethane sulfonate, indicating that Hnt3 and LP-BER provide parallel pathways for processing 5'-AMPs. Loss of HNT3 also increases the sister chromatid exchange frequency. HNT3 deletion partially rescues H2O2 sensitivity in recombination deficient rad51DELTA and rad52DELTA cells, suggesting that Hnt3 promotes formation of a repair intermediate that is resolved by recombination. Expression of Myc-NLS-tagged human aprataxin from a plasmid complements HNT3 deletion | Saccharomyces cerevisiae |
physiological function | aprataxin (APTX) is a DNA-adenylate hydrolase that removes 5'-AMP blocking groups from abortive ligation repair intermediates. Primary role of aprataxin is processing of adenylated 5' ends. XRCC1, a multi-domain protein without catalytic activity, interacts with a number of known repair proteins including APTX, modulating and coordinating the various steps of DNA repair. CK2- phosphorylation of XRCC1 is thought to be crucial for its interaction with the FHA domain of APTX. A phosphorylated XRCC1 is required for APTX recruitment.No interaction of APTX with a phosphorylation mutant of XRCC1 | Homo sapiens |
physiological function | Hnt3 promotes formation of a repair intermediate that is resolved by recombination. Hnt3 and LP-BER provide parallel pathways for processing 5'-AMPs, and Hnt3 promotes formation of a repair intermediate that is resolved by recombination. Lack of evidence for Hnt3 involvement in nonhomologous end joining | Saccharomyces cerevisiae |