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physiological function
3'-phosphate RNA ligase RtcB3 caps DNA and RNA 5'-PO4 ends to form GppDNA and GppRNA products, respectively. GppDNA formed by RtcB3 can be decapped to pDNA by the DNA repair enzyme aprataxin
physiological function
aprataxin interacts with the repair proteins XRCC1, PARP-1 and p53 and colocalizes with XRCC1 along charged particle tracks on chromatin
physiological function
FLJ20157
aprataxin is directly involved in DNA single-strand-break repair
physiological function
APTX interacts with X-ray repair cross-complementing group XRCC1, which has an essential role in single-strand DNA break repair. The 20 N-terminal amino acids of the forkhead-associated FHA-domain of APTX are important for its interaction with the C-terminal region (residues 492574) of XRCC1. Poly(ADPribose) polymerase PARP-1 is also co-immunoprecipitated with APTX
physiological function
-
deletion of the Saccharomyces cerevisiae Hnt3 gene, which encodes the aprataxin homolog, in combination with known DNA repair genes. While Hnt3 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 lack of Apn1, Apn2, Tpp1 and Ntg1, Ntg2, Ogg1. Loss of HNT3 in Rad27 mutant cells, which are deficient in long-patch base excision repair, results in synergistic sensitivity to H2O2 and methylmethane sulfonate. Loss of Hnt3 also increases the sister chromatid exchange frequency. Hnt3 deletion partially rescues H2O2 sensitivity in recombination-deficient mutant Rad51 and mutant Rad52 cells
physiological function
interaction between aprataxin and nucleolin occurs through their respective N-terminal regions. In cells from patients with ataxia with oculomotor apraxia type 1, AOA1, lacking aprataxin, the stability of nucleolin is significantly reduced. Down-regulation of nucleolin by RNA interference does not affect aprataxin protein levels but abolishes its nucleolar localization
physiological function
poly-ADP ribose polymerase PARP-1 is required in the recruitment of aprataxin to sites of DNA breaks. Inhibition of PARP activity does not affect aprataxin activity in vitro, it retards its recruitment to sites of DNA damage in vivo
physiological function
the long-form but not the short-form aprataxin interacts with x-ray repair cross-complementing group XRCC1. Aprataxin and XRCC1 may constitute a multiprotein complex and are involved in single-strand DNA break repair
physiological function
the protein is composed of three domains that share distant homology with the amino-terminal domain of polynucleotide kinase 3'-phosphatase, with histidine-triad proteins and with DNA-binding C2H2 zinc-finger proteins, respectively
physiological function
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APTX suppresses DNA-ligase 1-catalyzed ligation of 8oxoG-containing DNA. In presence of APTX, the catalytic commitment of DNA ligase 1 to erroneous ligation is reduced by 70 and 90%, respectively, for the 8oxoG:A and 8oxoG:C substrates
physiological function
depletion of aprataxin in human SHSY5Y neuroblastoma cells and primary skeletal muscle myoblasts results in mitochondrial dysfunction, revealed by reduced citrate synthase activity and mtDNA copy number. mtDNA, not nuclear DNA, has higher levels of background DNA damage on aprataxin knockdown
physiological function
-
3'-phosphate RNA ligase RtcB3 caps DNA and RNA 5'-PO4 ends to form GppDNA and GppRNA products, respectively. GppDNA formed by RtcB3 can be decapped to pDNA by the DNA repair enzyme aprataxin
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689insT
recessive mutation associated with ataxia and oculomotor apraxia, huge loss in protein stability
840delT
recessive mutation associated with ataxia and oculomotor apraxia, huge loss in protein stability
A198V
recessive mutation associated with ataxia and oculomotor apraxia, huge loss in protein stability
D267G
recessive mutation associated with ataxia and oculomotor apraxia, huge loss in protein stability
H260A
recessive mutation associated with ataxia and oculomotor apraxia, huge loss in protein stability
H260N
-
catalytically inactive
K197Q
recessive mutation associated with ataxia but not oculomotor apraxia, mild presentation allele
P206L
recessive mutation associated with ataxia and oculomotor apraxia, huge loss in protein stability
R199H
recessive mutation associated with ataxia and oculomotor apraxia, protein retains substantial function, consistent with altered activity
T739C
FLJ20157
homozygous mutation idientified in a patient with ataxia-oculomotor apraxia type 1
V263G
recessive mutation associated with ataxia and oculomotor apraxia, huge loss in protein stability
W279R
recessive mutation associated with ataxia and oculomotor apraxia, huge loss in protein stability
W279X
recessive mutation associated with ataxia and oculomotor apraxia, huge loss in protein stability
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medicine
ataxia-oculomotor apraxia, AOA1, is a neurological disorder with symptoms that overlap those of ataxiatelangiectasia, characterized by abnormal responses to double-strand DNA breaks and genome instability. The gene mutated in AOA1, APTX, codes for aprataxin which contains domains of homology with proteins involved in DNA damage signalling and repair. Cells from AOA1 show 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
medicine
cells from patients with ataxia oculomotor apraxia AOA1 show reduced expression of poly-ADP ribose polymerase PARP-1, apurinic endonuclease APE1 and N-glycosylase/DNA lyase OGG1. AOA1 cells exhibit elevated levels of oxidative DNA damage coupled with reduced base excision and gap filling repair efficiencies
medicine
FLJ20157
cells of an ataxia-oculomotor apraxia type 1 patient, homozygous for aprataxin mutation T739C, treated with camptothecin, inhibitor of DNA topoisomerase I which induces DNA single-strand breaks, show marked and dose-related increases in induced chromosomal aberrations compared to the intrafamilial wild-type control
medicine
in cells from patients with ataxia with oculomotor apraxia type 1, AOA1, lacking aprataxin, the stability of nucleolin is significantly reduced
medicine
mutations in aprataxin cause ataxiaocular apraxia 1, leading to early onset ataxia, oculomotor apraxia and cerebellar atrophy as well as axonal motor neuropathy and the later decrease of serum albumin levels and elevation of total cholesterol
medicine
in bone marrow of patients from a phase 2 study of the farnesyltransferase inhibitor tipifarnib in older adults with previously untreated acute myeloid leukemia, te RASGRP1/APTX gene expression ratio predicts response to tipifarnib with the greatest accuracy. RASGRP1 is a guanine nucleotide exchange factor that activates RAS, while APTX (aprataxin) is involved in DNA excision repair
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Harris, J.L.; Jakob, B.; Taucher-Scholz, G.; Dianov, G.L.; Becherel, O.J.; Lavin, M.F.
Aprataxin, poly-ADP ribose polymerase 1 (PARP-1) and apurinic endonuclease 1 (APE1) function together to protect the genome against oxidative damage
Hum. Mol. Genet.
18
4102-4117
2009
Homo sapiens (Q7Z2E3)
brenda
Sano, Y.; Date, H.; Igarashi, S.; Onodera, O.; Oyake, M.; Takahashi, T.; Hayashi, S.; Morimatsu, M.; Takahashi, H.; Makifuchi, T.; Fukuhara, N.; Tsuji, S.
Aprataxin, the causative protein for EAOH is a nuclear protein with a potential role as a DNA repair protein
Ann. Neurol.
55
241-249
2004
Homo sapiens (Q7Z2E3)
brenda
Date, H.; Igarashi, S.; Sano, Y.; Takahashi, T.; Takahashi, T.; Takano, H.; Tsuji, S.; Nishizawa, M.; Onodera, O.
The FHA domain of aprataxin interacts with the C-terminal region of XRCC1
Biochem. Biophys. Res. Commun.
325
1279-1285
2004
Homo sapiens (Q7Z2E3)
brenda
Mosesso, P.; Piane, M.; Palitti, F.; Pepe, G.; Penna, S.; Chessa, L.
The novel human gene aprataxin is directly involved in DNA single-strand-break repair
Cell. Mol. Life Sci.
62
485-491
2005
Homo sapiens (FLJ20157)
brenda
Daley, J.M.; Wilson, T.E.; Ramotar, D.
Genetic interactions between HNT3/aprataxin and RAD27/FEN1 suggest parallel pathways for 5' end processing during base excision repair
DNA Repair
9
690-699
2010
Saccharomyces cerevisiae
brenda
Gueven, N.; Becherel, O.J.; Kijas, A.W.; Chen, P.; Howe, O.; Rudolph, J.H.; Gatti, R.; Date, H.; Onodera, O.; Taucher-Scholz, G.; Lavin, M.F.
Aprataxin, a novel protein that protects against genotoxic stress
Hum. Mol. Genet.
13
1081-1093
2004
Homo sapiens (Q7Z2E3)
brenda
Becherel, O.J.; Gueven, N.; Birrell, G.W.; Schreiber, V.; Suraweera, A.; Jakob, B.; Taucher-Scholz, G.; Lavin, M.F.
Nucleolar localization of aprataxin is dependent on interaction with nucleolin and on active ribosomal DNA transcription
Hum. Mol. Genet.
15
2239-2249
2006
Homo sapiens (Q7Z2E3)
brenda
Maughan, W.P.; Shuman, S.
Characterization of 3-phosphate RNA ligase paralogs RtcB1, RtcB2, and RtcB3 from Myxococcus xanthus highlights DNA and RNA 5'-phosphate capping activity of RtcB3
J. Bacteriol.
197
3616-3624
2015
Schizosaccharomyces pombe (O74859), Schizosaccharomyces pombe 972 (O74859)
brenda
Seidle, H.F.; Bieganowski, P.; Brenner, C.
Disease-associated mutations inactivate AMP-lysine hydrolase activity of aprataxin
J. Biol. Chem.
280
20927-20931
2005
Homo sapiens (Q7Z2E3)
brenda
Moreira, M.C.; Barbot, C.; Tachi, N.; Kozuka, N.; Uchida, E.; Gibson, T.; Mendonca, P.; Costa, M.; Barros, J.; Yanagisawa, T.; Watanabe, M.; Ikeda, Y.; Aoki, M.; Nagata, T.; Coutinho, P.; Sequeiros, J.; Koenig, M.
The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin
Nat. Genet.
29
189-193
2001
Homo sapiens (Q7Z2E3)
brenda
Chauleau, M.; Jacewicz, A.; Shuman, S.
DNA3pp5G de-capping activity of aprataxin: effect of cap nucleoside analogs and structural basis for guanosine recognition
Nucleic Acids Res.
43
6075-6083
2015
Schizosaccharomyces pombe (O74859), Schizosaccharomyces pombe ATCC 24843 (O74859)
brenda
Raponi, M.; Lancet, J.E.; Fan, H.; Dossey, L.; Lee, G.; Gojo, I.; Feldman, E.J.; Gotlib, J.; Morris, L.E.; Greenberg, P.L.; Wright, J.J.; Harousseau, J.L.; Loewenberg, B.; Stone, R.M.; De Porre, P.; Wang, Y.; Karp, J.E.
A 2-gene classifier for predicting response to the farnesyltransferase inhibitor tipifarnib in acute myeloid leukemia
Blood
111
2589-2596
2008
Homo sapiens (Q7Z2E3)
brenda
Tumbale, P.; Jurkiw, T.; Schellenberg, M.; Riccio, A.; O'Brien, P.; Williams, R.
Two-tiered enforcement of high-fidelity DNA ligation
Nat. Commun.
10
5431
2019
Homo sapiens
brenda
Sykora, P.; Croteau, D.L.; Bohr, V.A.; Wilson, D.M.
Aprataxin localizes to mitochondria and preserves mitochondrial function
Proc. Natl. Acad. Sci. USA
108
7437-7442
2011
Homo sapiens (Q7Z2E3)
brenda