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Literature summary for 3.2.1.143 extracted from

  • Kim, I.; Stegeman, R.; Brosey, C.; Ellenberger, T.
    A quantitative assay reveals ligand specificity of the DNA scaffold repair protein XRCC1 and efficient disassembly of complexes of XRCC1 and the poly(ADP-ribose) polymerase 1 by poly(ADP-ribose) glycohydrolase (2015), J. Biol. Chem., 290, 3775-3783 .
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Cloned(Commentary)

Cloned (Comment) Organism
gene PARG, recombinant expression of wild-type enzyme and catalytically inactive mutant E752N, both comprising residues 385-972, in Escherichia coli strain Tuner (DE3) cells, coexpression of GroESL chaperone Rattus norvegicus

Protein Variants

Protein Variants Comment Organism
E752N site-directed mutagenesis, catalytically inactive mutant Rattus norvegicus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
PARP1-XRCC1 + H2O Rattus norvegicus efficient disassembly of complexes of the DNA scaffold repair protein XRCC1 and the poly(ADP-ribose) polymerase 1 by poly(ADP-ribose) glycohydrolase (PARG) ?
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Organism

Organism UniProt Comment Textmining
Rattus norvegicus Q9QYM2
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information quantitative, real-time assay of PAR-dependent protein-protein interactions and PAR turnover by PARG. PARG degrades the PAR posttranslational modification by a combination of exo- and endo-glycohydrolase activity, leaving a single ADP-ribose moiety attached to PARP1 that is a substrate for the mono(ADP-ribose) (MAR) hydrolases Rattus norvegicus ?
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PARP1-XRCC1 + H2O efficient disassembly of complexes of the DNA scaffold repair protein XRCC1 and the poly(ADP-ribose) polymerase 1 by poly(ADP-ribose) glycohydrolase (PARG) Rattus norvegicus ?
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PARP1-XRCC1 + H2O PARG rapidly reverses the PARylation of PARP1 and efficiently disassembles the PARP1-XRCC1 complex Rattus norvegicus ?
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Synonyms

Synonyms Comment Organism
PAR glycohydrolase
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 Rattus norvegicus
PARG
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 Rattus norvegicus

General Information

General Information Comment Organism
malfunction a deficiency in PARG glycohydrolase activity prolongs DNA damage foci, containing PAR, and similarly delays DNA repair, causing hypersensitivity to DNA damaging agents and selective killing of repair-deficient tumors such as BRCA mutated breast cancers-deficient cancer cells in a manner similar to PARP inhibition Rattus norvegicus
additional information quantitative, real-time assay of PAR-dependent protein-protein interactions and PAR turnover by PARG is an excellent tool for high-throughput screening to identify pharmacological modulators of PAR metabolism that Rattus norvegicus
physiological function the PAR posttranslational modification by itself is a high affinity ligand for XRCC1, requiring a minimum chain length of 7 ADP-ribose units in the oligo(ADP-ribose) ligand for a stable interaction with XRCC1. This discrete binding interface enables the poly(ADP-ribose) (PAR) glycohydrolase (PARG) to completely disassemble the PARP1-XRCC1 complex without assistance from a mono(ADP-ribose) glycohydrolase. XRCC1 and other PAR-binding proteins mediate many of the downstream responses to PARP1 activation in the face of DNA damage. PARG rapidly reverses the PARylation of PARP1 and efficiently disassembles the PARP1-XRCC1 complex, thereby uncoupling the DNA repair scaffolding activities of XRCC1 from PARP1, which is targeted for proteasomal degradation after recruiting XRCC1 to sites of DNA damage. Ability of PARG to regulate the PARP1-XRCC1 interaction by converting PARylated PARP1 into MARylated PARP1, which retains a terminal ADP-ribose modification but does not bind to XRCC1 Rattus norvegicus