Reaction participants Show >> << Hide
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Namehelp_outline
a 5'-end adenosine-5'-diphospho-5'-ribonucleoside-2'-deoxyribonucleotide-DNA
Identifier
RHEA-COMP:13182
Reactive part
help_outline
- Name help_outline adenosine-5'-diphospho-5'-ribonucleotide-(2'-deoxyribonucleotide) residue Identifier CHEBI:136414 Charge -3 Formula C20H26N5O18P3R2 SMILEShelp_outline *[C@@H]1O[C@H](COP(=O)(OP(=O)(OC[C@H]2O[C@@H](N3C=4N=CN=C(N)C4N=C3)[C@@H]([C@@H]2O)O)[O-])[O-])[C@@H](OP(OC[C@H]5O[C@@H](*)C[C@@H]5O*)(=O)[O-])[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H2O Identifier CHEBI:15377 (Beilstein: 3587155; CAS: 7732-18-5) help_outline Charge 0 Formula H2O InChIKeyhelp_outline XLYOFNOQVPJJNP-UHFFFAOYSA-N SMILEShelp_outline [H]O[H] 2D coordinates Mol file for the small molecule Search links Involved in 6,048 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
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Namehelp_outline
a 5'-end 5'-monophospho-ribonucleoside-2'-deoxyribonucleotide-DNA
Identifier
RHEA-COMP:13183
Reactive part
help_outline
- Name help_outline 5'-phosphate ribonucleotide-(2'-deoxyribonucleotide) residue Identifier CHEBI:136415 Charge -3 Formula C10H14O12P2R2 SMILEShelp_outline *[C@@H]1O[C@H](COP(=O)([O-])[O-])[C@@H](OP(OC[C@H]2O[C@@H](*)C[C@@H]2O*)(=O)[O-])[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline AMP Identifier CHEBI:456215 Charge -2 Formula C10H12N5O7P InChIKeyhelp_outline UDMBCSSLTHHNCD-KQYNXXCUSA-L SMILEShelp_outline Nc1ncnc2n(cnc12)[C@@H]1O[C@H](COP([O-])([O-])=O)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 487 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,176 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
RHEA:52132 | RHEA:52133 | RHEA:52134 | RHEA:52135 | |
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Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
UniProtKB help_outline |
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EC numbers help_outline | ||||
MetaCyc help_outline |
Publications
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The neurodegenerative disease protein aprataxin resolves abortive DNA ligation intermediates.
Ahel I., Rass U., El-Khamisy S.F., Katyal S., Clements P.M., McKinnon P.J., Caldecott K.W., West S.C.
Ataxia oculomotor apraxia-1 (AOA1) is a neurological disorder caused by mutations in the gene (APTX) encoding aprataxin. Aprataxin is a member of the histidine triad (HIT) family of nucleotide hydrolases and transferases, and inactivating mutations are largely confined to this HIT domain. Aprataxi ... >> More
Ataxia oculomotor apraxia-1 (AOA1) is a neurological disorder caused by mutations in the gene (APTX) encoding aprataxin. Aprataxin is a member of the histidine triad (HIT) family of nucleotide hydrolases and transferases, and inactivating mutations are largely confined to this HIT domain. Aprataxin associates with the DNA repair proteins XRCC1 and XRCC4, which are partners of DNA ligase III and ligase IV, respectively, suggestive of a role in DNA repair. Consistent with this, APTX-defective cell lines are sensitive to agents that cause single-strand breaks and exhibit an increased incidence of induced chromosomal aberrations. It is not, however, known whether aprataxin has a direct or indirect role in DNA repair, or what the physiological substrate of aprataxin might be. Here we show, using purified aprataxin protein and extracts derived from either APTX-defective chicken DT40 cells or Aptx-/-mouse primary neural cells, that aprataxin resolves abortive DNA ligation intermediates. Specifically, aprataxin catalyses the nucleophilic release of adenylate groups covalently linked to 5'-phosphate termini at single-strand nicks and gaps, resulting in the production of 5'-phosphate termini that can be efficiently rejoined. These data indicate that neurological disorders associated with APTX mutations may be caused by the gradual accumulation of unrepaired DNA strand breaks resulting from abortive DNA ligation events. << Less
Nature 443:713-716(2006) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.
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Aprataxin resolves adenylated RNA-DNA junctions to maintain genome integrity.
Tumbale P., Williams J.S., Schellenberg M.J., Kunkel T.A., Williams R.S.
Faithful maintenance and propagation of eukaryotic genomes is ensured by three-step DNA ligation reactions used by ATP-dependent DNA ligases. Paradoxically, when DNA ligases encounter nicked DNA structures with abnormal DNA termini, DNA ligase catalytic activity can generate and/or exacerbate DNA ... >> More
Faithful maintenance and propagation of eukaryotic genomes is ensured by three-step DNA ligation reactions used by ATP-dependent DNA ligases. Paradoxically, when DNA ligases encounter nicked DNA structures with abnormal DNA termini, DNA ligase catalytic activity can generate and/or exacerbate DNA damage through abortive ligation that produces chemically adducted, toxic 5'-adenylated (5'-AMP) DNA lesions. Aprataxin (APTX) reverses DNA adenylation but the context for deadenylation repair is unclear. Here we examine the importance of APTX to RNase-H2-dependent excision repair (RER) of a lesion that is very frequently introduced into DNA, a ribonucleotide. We show that ligases generate adenylated 5' ends containing a ribose characteristic of RNase H2 incision. APTX efficiently repairs adenylated RNA-DNA, and acting in an RNA-DNA damage response (RDDR), promotes cellular survival and prevents S-phase checkpoint activation in budding yeast undergoing RER. Structure-function studies of human APTX-RNA-DNA-AMP-Zn complexes define a mechanism for detecting and reversing adenylation at RNA-DNA junctions. This involves A-form RNA binding, proper protein folding and conformational changes, all of which are affected by heritable APTX mutations in ataxia with oculomotor apraxia 1. Together, these results indicate that accumulation of adenylated RNA-DNA may contribute to neurological disease. << Less
Nature 506:111-115(2014) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.