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evolution
canonical poly(ADP-ribose) glycohydrolase is a highly conserved protein found in organisms ranging from protozoa to humans, phylogenetic analysis. The full-length enzyme from Tetrahymena thermophila is highly similar to the minimal catalytic region of thhe human enzyme, but it lacks the obvious RS/MTS motif
evolution
conservation of key residues involved in the catalytic process
evolution
conservation of overall fold amongst mammalian enzyme glycohydrolase domains, additional flexible regions in the catalytic site, overview
evolution
full-length ARH3 (ARH3FL) adopts a compact all-alpha-helical fold with a central deep ADPR-binding cleft, a signature of the ARH3 superfamily
evolution
function and domain architecture of human ADP-ribosylation removing enzymes, overview. The key poly(ADP-ribose) (PAR) processing enzyme, PARG, emerged only recently
malfunction
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osmotic (mannitol treatment) or oxidative (methyl viologen treatment) stress reduces germination rates of the mutant parg1-3 seeds compared with wild type seeds. The parg1-3 plants show reduced tolerance to drought (withholding water), osmotic, and oxidative stress, as well as increased levels of cell damage under osmotic and oxidative stress and reduced survival under drought stress when compared with the wild type plants. Stomata of the parg1-3 plants fail to close under drought stress conditions
malfunction
benzo(a)pyrene induces the cell cycle in enzyme-suppressed shPARG cells, phenotype, overview
malfunction
enzyme deficiency leads to cell death whilst enzyme depletion causes sensitisation to certain DNA damaging agents
malfunction
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genetic disruption of the enzyme leads to increased level of cell death by accumulation of poly(ADP-ribose)
malfunction
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knockout mutants of isozyme PARG110 show resistance to photoreceptor degeneration, the mutant retina is morphologically and functionally undistinguishable from wild-type. Absence of PARG110 disrupts the poly-ADP-ribose polymerase activation
malfunction
lack of poly(ADPribose) glycohydrolase activity in Vero and A549 host cells, achieved by chemical inhibition or iRNA, produces the reduction of the percentage of infected cells as well as the number of amastigotes per cell and trypomastigotes released, leading to a nearly complete abrogation of the infection process
malfunction
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poly(ADP-ribose) glycohydrolase loss-of-function causes increased Hrp38 poly(ADP-ribosyl)ation and also results in the rough-eye phenotype with disrupted ommatidial lattice and and bristles and reduced number of photoreceptor cells. Hrp38 is essential for fly eye development. Parg mutant eye clones have decreased expression level of DE-cadherin with orientation defects, which is reminiscent of DE-cadherin mutant eye phenotype. The Parg mutant eye accumulates a large amount of poly(ADP-ribose)
malfunction
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RNAi knockdown of PARG or pretreatment with 2-((R)-2-methylpyrrolidin-2-yl)-1H-benzimidazole-4-carboxamide (ABT-888), meaning an increase in poly(ADP-ribose) level, lead to increased HeLa cell death in N-methyl-N'-nitro-N-nitrosoguanidine-treated HeLa cells. The effect can be reduced by PARP-1 inhibitors. Combination of poly(ADP-ribose) polymerase-1 and poly(ADP-ribose) glycohydrolase inhibition in chemotherapy does not produce increased HeLa cell death
malfunction
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silencing of endogenous enzyme expression causes inhibition of TGFbeta-mediated transcription. This can be relieved after simultaneous depletion of poly(ADP-ribose) polymerase 1
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
malfunction
disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. Endogenous PAR levels in Deinococcus radiodurans are elevated after UV irradiation, indicating that the prokaryotic PARylation may be involved in resistance to genotoxic stresses
malfunction
mutation of PARG1 results in increased DNA damage level and enhanced cell death in plants after bleomycin treatment. Inhibition or silencing of PARPs improves abiotic stress tolerance, enhancing resistance to drought, high light, heat and oxidative stresses, and perturbs innate immune responses to microbe-associated molecular patterns such as flg22 and elf18, resulting in a compromised basal defense response. Phenotypic comparison of the loss-of-function mutants of all PARP and PARG genes in Arabidopsis thaliana, overview. Loss-of-PARG1 leads to the transcriptional up-regulation of DNA repair genes and increase of cellular DNA damage level. The parg1 mutants show only yellow instead of green seedlings with reduced fresh weight compared to wild-type. The parg1-4 mutant root is more sensitive to bleomycin than that of wild-type Col-0
malfunction
PARG inhibition increases endogenous DNA damage, stalls replication forks and increases homologous recombination, and the lack of homologous recombination (HR) proteins at PARG inhibitor-induced stalled replication forks induces cell death. siRNA screen for increased DNA damage with PARG depletion. Model whereby inhibition or depletion of PARG leads to fork stalling and fork aberrations, resulting in signalling and recruitment of HRR proteins for repair. Therefore in the absence of these homologous recombination repair (HRR) proteins, PARG depleted or inhibited cells cannot survive
malfunction
poly(ADP-ribose) glycohydrolase (PARG) silencing suppresses benzo(a)pyrene induced cell transformation. Benzo(a)pyrene (BaP) is a ubiquitously distributed environmental pollutant and known carcinogen, which can induce malignant transformation in cells. PARG silencing dramatically reduces DNA damages, chromosome abnormalities, and micronuclei formations in the PARG-deficient human bronchial epithelial cells compared to the control 16HBE cells. PARG silencing down-regulates cell colony formation induced by BaP, reduces BaP-induced genomic instability, and protects cells from BaP-induced DNA damage
malfunction
poly(ADP-ribosyl) glycohydrolase (PARG) depletion affects cell proliferation and DNA synthesis, leading to replication-coupled H2AX phosphorylation. PARG depletion or inhibition per se slows down individual replication forks similarly to mild chemotherapeutic treatment. Electron microscopic analysis of replication intermediates reveals marked accumulation of reversed forks and single-stranded DNA (ssDNA) gaps in unperturbed PARG-defective cells. PARG-defective cells display both ataxia-telangiectasia-mutated (ATM) and ataxia-Rad3-related (ATR) activation, as well as chromatin recruitment of standard double-strand-break-repair factors, such as 53BP1 and RAD51, but no physical evidence for chromosomal breakage. PARG-deficient cell phenotype, detailed overview. PARG depletion results in slow replication fork progression even in the absence of genotoxic treatments. PARG downregulation and inhibition lead to similar phenotypic consequences
malfunction
the wild-type strain with or without H2O2 shows no evident changes in the randomly amplified polymorphic DNA, RAPD, pattern. The mutant DELTAparg strain, in the presence of H2O2, exhibits a reduced pattern, suggesting that DNA is damaged in this strain and repair is impaired. No morphological differences in color, growth rate or morphology are observed for the mutant strain on solid medium as compared with the wild-type strain
malfunction
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the wild-type strain with or without H2O2 shows no evident changes in the randomly amplified polymorphic DNA, RAPD, pattern. The mutant DELTAparg strain, in the presence of H2O2, exhibits a reduced pattern, suggesting that DNA is damaged in this strain and repair is impaired. No morphological differences in color, growth rate or morphology are observed for the mutant strain on solid medium as compared with the wild-type strain
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malfunction
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disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. Endogenous PAR levels in Deinococcus radiodurans are elevated after UV irradiation, indicating that the prokaryotic PARylation may be involved in resistance to genotoxic stresses
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malfunction
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the wild-type strain with or without H2O2 shows no evident changes in the randomly amplified polymorphic DNA, RAPD, pattern. The mutant DELTAparg strain, in the presence of H2O2, exhibits a reduced pattern, suggesting that DNA is damaged in this strain and repair is impaired. No morphological differences in color, growth rate or morphology are observed for the mutant strain on solid medium as compared with the wild-type strain
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malfunction
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the wild-type strain with or without H2O2 shows no evident changes in the randomly amplified polymorphic DNA, RAPD, pattern. The mutant DELTAparg strain, in the presence of H2O2, exhibits a reduced pattern, suggesting that DNA is damaged in this strain and repair is impaired. No morphological differences in color, growth rate or morphology are observed for the mutant strain on solid medium as compared with the wild-type strain
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malfunction
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the wild-type strain with or without H2O2 shows no evident changes in the randomly amplified polymorphic DNA, RAPD, pattern. The mutant DELTAparg strain, in the presence of H2O2, exhibits a reduced pattern, suggesting that DNA is damaged in this strain and repair is impaired. No morphological differences in color, growth rate or morphology are observed for the mutant strain on solid medium as compared with the wild-type strain
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malfunction
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mutation of PARG1 results in increased DNA damage level and enhanced cell death in plants after bleomycin treatment. Inhibition or silencing of PARPs improves abiotic stress tolerance, enhancing resistance to drought, high light, heat and oxidative stresses, and perturbs innate immune responses to microbe-associated molecular patterns such as flg22 and elf18, resulting in a compromised basal defense response. Phenotypic comparison of the loss-of-function mutants of all PARP and PARG genes in Arabidopsis thaliana, overview. Loss-of-PARG1 leads to the transcriptional up-regulation of DNA repair genes and increase of cellular DNA damage level. The parg1 mutants show only yellow instead of green seedlings with reduced fresh weight compared to wild-type. The parg1-4 mutant root is more sensitive to bleomycin than that of wild-type Col-0
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malfunction
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disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. Endogenous PAR levels in Deinococcus radiodurans are elevated after UV irradiation, indicating that the prokaryotic PARylation may be involved in resistance to genotoxic stresses
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malfunction
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disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. Endogenous PAR levels in Deinococcus radiodurans are elevated after UV irradiation, indicating that the prokaryotic PARylation may be involved in resistance to genotoxic stresses
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malfunction
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disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. Endogenous PAR levels in Deinococcus radiodurans are elevated after UV irradiation, indicating that the prokaryotic PARylation may be involved in resistance to genotoxic stresses
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malfunction
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disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. Endogenous PAR levels in Deinococcus radiodurans are elevated after UV irradiation, indicating that the prokaryotic PARylation may be involved in resistance to genotoxic stresses
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malfunction
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disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. Endogenous PAR levels in Deinococcus radiodurans are elevated after UV irradiation, indicating that the prokaryotic PARylation may be involved in resistance to genotoxic stresses
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malfunction
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disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. Endogenous PAR levels in Deinococcus radiodurans are elevated after UV irradiation, indicating that the prokaryotic PARylation may be involved in resistance to genotoxic stresses
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malfunction
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disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. Endogenous PAR levels in Deinococcus radiodurans are elevated after UV irradiation, indicating that the prokaryotic PARylation may be involved in resistance to genotoxic stresses
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metabolism
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isozyme PARG110 and poly-ADP-ribose polymerase-1 act in a positive feedback loop, which is especially active under pathologic conditions
metabolism
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molecular mechanism(s) connecting poly(ADP-ribosyl)ation with DNA methylation, giving a possible explanation as to how DNA methylation modulates by poly(ADP-ribosyl)ation as the posttranslational modification. DNA methyltransferases also interact with poly(ADP-D-ribose)
metabolism
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poly(ADP-ribose) glycohydrolase partly controls the turnover of dynamic protein ADP-ribosylation mediated by poly(ADP-ribose) polymerase 1, PARP-1. Poly(ADP-ribose) glycohydrolase (PARG) can remove poly(ADP-ribose) chains from target proteins of PARP-1. Endogenous PARP-1 and the enzyme have opposing roles on TGFbeta-induced gene expression, overview
metabolism
PARP-dependent ADP-ribosylation cycle involving enzyme PARG
metabolism
poly(ADP-ribosyl)ation is a reversible post-translational modification of proteins, characterized by the addition of poly(ADP-ribose) (PAR) to proteins by poly(ADP-ribose) polymerase (PARP), and removal of PAR by poly(ADP-ribose) glycohydrolase (PARG). Three PARPs and two PARGs have been found in Arabidopsis thaliana. PARG1 and PARG2 play an essential and a minor role, respectively under the same conditions
metabolism
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poly(ADP-ribosyl)ation is a reversible post-translational modification of proteins, characterized by the addition of poly(ADP-ribose) (PAR) to proteins by poly(ADP-ribose) polymerase (PARP), and removal of PAR by poly(ADP-ribose) glycohydrolase (PARG). Three PARPs and two PARGs have been found in Arabidopsis thaliana. PARG1 and PARG2 play an essential and a minor role, respectively under the same conditions
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physiological function
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generation of A549 lung adenocarcinoma cell lines with stably suppressed PARG and poly(ADP-ribose) polymerase PARP-1 expression, i.e. shPARG and shPARP1 cell lines, respectively. shPARG cells accumulate large amounts of poly-(ADP-ribosyl)ated proteins and exhibit reduced PARP activation. Hydrogen peroxide-induced cell death is regulated by PARG in a dual fashion. Whereas the shPARG cell line is resistant to the necrotic effect of high concentrations of hydrogen peroxide, these cells exhibit stronger apoptotic response. Both shPARP1 and especially shPARG cells display a delayed repair of DNA breaks and exhibit reduced clonogenic survival following hydrogen peroxide treatment. Translocation of apoptosis-inducing factor cannot be observed, but cells can be saved by methyl pyruvate and alpha-ketoglutarate
physiological function
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homozygous T-DNA knockout line parg1 seedlings exhibit exaggerated seedling growth inhibition and pigment accumulation in response to elf18 and are hypersensitive to the DNA-damaging agent mitomycin C. Both parg1 and parg2 knockout plants show accelerated onset of disease symptoms when infected with Botrytis cinerea. Cellular levels of ADP-ribose polymer increase after infection with avirulent Pseudomonas syringae pv tomato DC3000 avrRpt2+, and pathogen-dependent changes in the poly(ADP-ribosyl)ation of discrete proteins are also observed
physiological function
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stable knock-down of poly(ADP-ribose) polymerase PARP-1 and PARG. The majority of genes affected by the knockdown of one factor are similarly affected by the knockdown of the other factor. The most robustly regulated common genes are enriched for stress-response and metabolic functions. PARP-1 and PARG localize to the promoters of positively and negatively regulated target genes. The levels of chromatin-bound PARG at a given promoter generally correlate with the levels of PARP-1 across the subset of promoters tested. For about half of the genes tested, the binding of PARP-1 at the promoter is dependent on the binding of PARG. PARP-1 and PARG enzymatic activities are required for some, but not all, target genes
physiological function
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Arabidopsis poly(ADP-ribose) glycohydrolase 1 is required for drought, osmotic and oxidative stress responses
physiological function
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at higher levels of DNA damage, the coordinate activities of PARPs-1/2 and PARG can rapidly deplete the pool of cellular NAD(H), facilitating the release of mitochondrial proteins through signaling pathways that promote cell death
physiological function
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coordinate regulation of PARP-1 and -2 and PARG is required for cellular responses to genotoxic stress
physiological function
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poly(ADP-ribose)glycohydrolase is an upstream regulator of Ca2+ fluxes in oxidative cell death. Transient receptor potential 2 is the primary Ca2+ channel for cell death signaling under poly(ADP-ribose)glycohydrolase control
physiological function
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by regulating the hydrolytic arm of poly(ADP-ribosyl)ation, the enzyme participates in a number of biological processes, including the repair of DNA damage, chromatin dynamics, transcriptional regulation, and cell death. Role of silencing of the enzyme in DNA methylation pattern changed by benzo(a)pyrene, a carcinogen cytotoxic which can trigger extensive cellular responses
physiological function
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causal involvement of wild-type isozyme PARG110 in the process of photoreceptor degeneration. Contrasting its anticipated role as a functional antagonist, absence of PARG110 correlated with low PARP activity, suggesting that PARG110 and PARP1 act in a positive feedback loop, which is especially active under pathologic conditions
physiological function
poly(ADP-ribose) glycohydrolase (PARG) represents the main poly(ADP-D-ribose) hydrolyzing activity in the cell to ADP-ribose units. The enzyme is crucial for Trypanosoma cruzi infection cycle in the human host cell. Both, Trypanosoma cruzi and the human host, poly(ADP-ribose) glycohydrolase activities are important players in the life cycle of Trypanosoma cruzi
physiological function
poly(ADP-ribose) glycohydrolase catalyzes the removal of poly(ADP-ribose) chains from posttranslationally modified proteins by hydrolysis of alpha(122-22) O-glycosidic linkages, functioning as an endo-glycosidase to release oligo(ADP-ribose) and as an exo-glycosidase to release ADP-ribose
physiological function
poly(ADP-ribosyl)ation is a crucial regulator of cell fate in response to genotoxic stress, poly(ADP-ribose) degradation is carried out mainly by poly(ADP-ribose) glycohydrolase, role of poly(ADP-ribose) glycohydrolase in the regulation of cell fate in response to benzo(a)pyrene, overview
physiological function
protein poly(ADP-ribosyl)ation regulates a number of important cellular processes. Poly(ADP-ribose) glycohydrolase is the primary enzyme responsible for hydrolyzing the poly(ADP-ribose) polymer in vivo
physiological function
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the enzyme activity regulates cellular poly(ADP-ribose) level. Since the enzyme cannot cleave the terminal ADP-ribose unit at the protein bound to glutamate residues, the residual activities of MacroD2 and TARG1 may contribute to the accumulation of poly(ADP-D-ribose)in the Parg knockout animals
physiological function
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the enzyme is responsible for the degradation of poly(ADP-ribose) (PAR) polymers
physiological function
the reversion of poly(ADP-ribosyl)ation is catalysed by poly(ADP-ribose) glycohydrolase, which specifically targets the unique PAR (1''-2') ribose-ribose bonds
physiological function
a single poly(ADP-ribosyl) glycohydrolase (PARG) mediates PAR degradation. PARG prevents the accumulation of unusual replication structures during unperturbed S phase. Role of PARG in the replication of human chromosomes. PAR degradation is essential to promote resumption of replication at endogenous and e-exogenous lesions, preventing idle recruitment of repair factors to remodeled replication forks
physiological function
degradation of poly(ADP-ribose), PAR, is catalyzed by poly(ADP-ribose) glycohydrolase (PARG) by endo- and exoglycosidase reactions that release products of variable length and ADPribose monomers. The poly(ADP-ribosyl) glycohydrolase, PARG, protein of Fusarium oxysporum f. sp. lycopersici is involved in DNA repair and does not act in pathogenicity as an effector. The organism encodes for only one PARG enzyme, and this is responsible for the total cellular PARG activity
physiological function
enzyme ARH3 is a multifunctional enzyme that also hydrolyzes poly(ADP-ribose) (ADPR). Enzyme ARH3 plays a role in DNA damage repair. The recruitment of ARH3 to DNA lesions is mediated by ADPR recognition. The catalytic mechanism of protein ADP-ribose hydrolases can be classified into two different groups, namely metal-dependent and metal-independent catalysis. ARHs, such as ARH3, belong to metal-dependent catalysis, utilizing two Mg2+ ions and acidic residues to complete the catalytic reaction, which might be highly conserved. In contrast, the catalytic mechanism is not conserved in the macrodomain ADP-ribose hydrolases, For example, Glu756 and a water molecule act together to catalyze the reaction in PARG, whereas the key catalytic factor in MacroD2 is an activated water. The charge characteristic of the binding pocket in ARH3 is remarkably distinguished from that in PARG. The binding pocket of PARG, accommodating the ADPR dimer, is mostly composed of the basic region
physiological function
enzyme ARH3 is a multifunctional enzyme that also hydrolyzes poly(ADP-ribose) (PAR). ARH3 can specifically hydrolyze PAR, mono-ADP-ribose post-translational modifications (MARPTMs), and O-acetyl-ADP-ribose. For all these substrates, ARH3 preferentially hydrolyzes the scissile alpha-O-linkage attached to the anomeric C1'' position of ADPR. In mammals, two enzymes, ADP-ribosyl-acceptor hydrolase 3 (ARH3 or ADPRHL2) and PAR glycohydrolase (PARG), function in tandem to reverse PARylation. These hydrolytic enzymes commonly cleave the alpha(1''-2') O-glycosidic linkages in PAR chains. ARH3 appears to catalyze primarily exocytic cleavage of PAR, generating free ADPR. It is reported that ARH3 protects cells from oxidative stress-induced parthanatos by lowering the cytoplasmic PAR level. ARH3 is a distinctive, multitasking enzyme that controls two biologically important NAD+-dependent cellular signaling pathways
physiological function
PARG1 has poly(ADP-ribose) (PAR)-degrading activity and regulates poly(ADP-ribose) level in vivo. PARG1 and PARG2 play an essential and a minor role, respectively under the same conditions. PARG1 expression is induced primarily in root and shoot meristems by bleomycin and induction of PARG1 is dependent on ATM and ATR kinases. PARG1 antagonistically modulates the DNA repair process by preventing the over-induction of DNA repair genes. PARG1 plays a critical role in this process. Roles of PARP1 and PARP2 in DNA damage signaling. Induction of PARG1 gene is ATM- and ATR-dependent and PARG1 represses the transcriptional upregulation of ATM, ATR and SOG1. ATM and ATR are two critical kinases which transduce double and single strand break signals to DNA repair machinery, respectively. They phosphorylate the transcription factor SOG1, which then induces the expression of DNA repair genes
physiological function
poly(ADP-ribosyl)ation (PARylation) is a transient posttranslational modification that generates a signaling mechanism with diverse roles within molecular and cellular processes. PAR chains remaining from DNA repair are broken down by the enzyme poly(ADP-ribose) glycohydrolase (PARG). PARG catalyzes the hydrolysis of endo- and exoglycosidic bonds within the poly(ADP-ribose) (PAR) polymers
physiological function
poly(ADP-ribosyl)ation is a common post-translational modification that mediates a wide variety of cellular processes including DNA damage repair, chromatin regulation, transcription, and apoptosis, involving interactions of PAR with poly(ADP-ribose) glycohydrolase (PARG) and other binding proteins
physiological function
poly(ADP-ribosylation) of proteins follows DNA damage. Like addition of poly(ADP-ribose) (PAR) by poly(ADP-ribose) polymerase (PARP), removal of PAR by PARG is also thought to be required for repair of DNA strand breaks and for con-tinued replication at perturbed forks. Poly(ADP-ribose) glycohydrolase (PARG) has endo- and exoglycosidase activities which can cleaveglycosidic bonds, rapidly reversing the action of PARP enzymes. The functions of PARP and PARG may not be completely identical
physiological function
poly(ADPribose) glycohydrolase (PARG) is the primary enzyme that catalyzes the degradation of poly (ADP-ribose) (PAR), it plays an important role in regulating DNA damage repair and maintaining genomic stability
physiological function
the enzyme poly(ADP-ribose) glycohydrolase (PARG) performs a critical role in the repair of DNA single strand breaks (SSBs). Critical to this repair process is the orderly degradation of PAR chains. The roles of PARG and poly(ADP-ribose) polymerase (PARP) are closely intertwined
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
physiological function
the poly(ADP-ribose) glycohydrolase (PARG) endo-glycohydrolase activity may become significant in vivo at high PAR/PARG ratios (for example, in the case of an extreme cellular insult), thus releasing free PAR fragments to mediate apoptotic signaling
physiological function
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degradation of poly(ADP-ribose), PAR, is catalyzed by poly(ADP-ribose) glycohydrolase (PARG) by endo- and exoglycosidase reactions that release products of variable length and ADPribose monomers. The poly(ADP-ribosyl) glycohydrolase, PARG, protein of Fusarium oxysporum f. sp. lycopersici is involved in DNA repair and does not act in pathogenicity as an effector. The organism encodes for only one PARG enzyme, and this is responsible for the total cellular PARG activity
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physiological function
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degradation of poly(ADP-ribose), PAR, is catalyzed by poly(ADP-ribose) glycohydrolase (PARG) by endo- and exoglycosidase reactions that release products of variable length and ADPribose monomers. The poly(ADP-ribosyl) glycohydrolase, PARG, protein of Fusarium oxysporum f. sp. lycopersici is involved in DNA repair and does not act in pathogenicity as an effector. The organism encodes for only one PARG enzyme, and this is responsible for the total cellular PARG activity
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physiological function
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degradation of poly(ADP-ribose), PAR, is catalyzed by poly(ADP-ribose) glycohydrolase (PARG) by endo- and exoglycosidase reactions that release products of variable length and ADPribose monomers. The poly(ADP-ribosyl) glycohydrolase, PARG, protein of Fusarium oxysporum f. sp. lycopersici is involved in DNA repair and does not act in pathogenicity as an effector. The organism encodes for only one PARG enzyme, and this is responsible for the total cellular PARG activity
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physiological function
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degradation of poly(ADP-ribose), PAR, is catalyzed by poly(ADP-ribose) glycohydrolase (PARG) by endo- and exoglycosidase reactions that release products of variable length and ADPribose monomers. The poly(ADP-ribosyl) glycohydrolase, PARG, protein of Fusarium oxysporum f. sp. lycopersici is involved in DNA repair and does not act in pathogenicity as an effector. The organism encodes for only one PARG enzyme, and this is responsible for the total cellular PARG activity
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physiological function
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PARG1 has poly(ADP-ribose) (PAR)-degrading activity and regulates poly(ADP-ribose) level in vivo. PARG1 and PARG2 play an essential and a minor role, respectively under the same conditions. PARG1 expression is induced primarily in root and shoot meristems by bleomycin and induction of PARG1 is dependent on ATM and ATR kinases. PARG1 antagonistically modulates the DNA repair process by preventing the over-induction of DNA repair genes. PARG1 plays a critical role in this process. Roles of PARP1 and PARP2 in DNA damage signaling. Induction of PARG1 gene is ATM- and ATR-dependent and PARG1 represses the transcriptional upregulation of ATM, ATR and SOG1. ATM and ATR are two critical kinases which transduce double and single strand break signals to DNA repair machinery, respectively. They phosphorylate the transcription factor SOG1, which then induces the expression of DNA repair genes
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additional information
E748 and E749 are the key catalytic residues in the signature loop, N733 directly recognizes the 3'-OH on the proximal ribose, catalytic domain structure in apo- and liganded-states, overview. The N-terminal flexible peptide preceding the enzyme's catalytic domain may regulate the enzymatic activity, catalytic and regulatory mechanisms, overview. A binding site outside of the catalytic cleft for iso-ADP-ribose, which is probably the smallest enzyme subtrate containing the alpha(1->2) ribose-ribose glycosidic bond, may explain the processivity of the enzyme activity
additional information
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E748 and E749 are the key catalytic residues in the signature loop, N733 directly recognizes the 3'-OH on the proximal ribose, catalytic domain structure in apo- and liganded-states, overview. The N-terminal flexible peptide preceding the enzyme's catalytic domain may regulate the enzymatic activity, catalytic and regulatory mechanisms, overview. A binding site outside of the catalytic cleft for iso-ADP-ribose, which is probably the smallest enzyme subtrate containing the alpha(1->2) ribose-ribose glycosidic bond, may explain the processivity of the enzyme activity
additional information
enzyme structure overview
additional information
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enzyme structure overview
additional information
enzyme structure-function relationship, computational analysis based on the crystal structure, PDB ID 3SIG, modelling of active site structure and SN2 mechanism catalytic mechanism, overview. The oxocarbenium expected by Dea Slade is a possible transition state but not an intermediate.
additional information
structure analysis and comparisons, overview. The poorly structured A-domain does not contribute to PARG activity in vitro. The rPARG385 catalytic domain adopts a beanshaped structure with a deep central cleft containing the conserved PARG-signature motif (GGG-X6-8-QEE)10 and Tyr791 that contributes strongly to PARG catalytic efficiency and inhibitor binding. The active site cleft lies on one edge of the beta-sheet and an extended N-terminal segment containing the MTS wraps around the other edge of the beta-sheet, contributing to the PARG catalytic domain
additional information
structure-based mechanism for the reported endo- and exo-glycohydrolase activities in human enzyme, overview
additional information
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structure-based mechanism for the reported endo- and exo-glycohydrolase activities in human enzyme, overview
additional information
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the Glu752 residue plays an important role in the enzyme's catalytic activity by functioning as a general acid or base to protonate the 2'-OH of the ribose of the leaving group, and subsequently activating a water molecule for nucleophilic attack
additional information
analysis of the catalytic site structure of ARH3, overview
additional information
CD spectra of enzyme DrPARG in the absence and presence of ADP-ribose exhibit increased proportion of alpha-helices and beta-strands from 11.78% and 30.37% to 15.10% and 33.52%, respectively, which suggests that conformational changes occur during the binding of ADP-ribose. The intrinsically disordered N-terminal region of DrPARG might be highly flexible. ADP-ribose binding pocket and complex structure, and conformational effects, detailed overview
additional information
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CD spectra of enzyme DrPARG in the absence and presence of ADP-ribose exhibit increased proportion of alpha-helices and beta-strands from 11.78% and 30.37% to 15.10% and 33.52%, respectively, which suggests that conformational changes occur during the binding of ADP-ribose. The intrinsically disordered N-terminal region of DrPARG might be highly flexible. ADP-ribose binding pocket and complex structure, and conformational effects, detailed overview
additional information
proposed catalytic role of residue Asp314. Asp314 is located proximal to the 1''-O-linkage in substrates. Asp314 might protonate the leaving group (general acid), forming an oxocarbenium ion intermediate, and then activate the water (general base) for back-side attack. The W1 ligand of MgB can serve as the nucleophile attacking the anomeric C1'' of the ribose''. This is consistent with the observed O18 incorporation during hydrolysis of O-acetyl-ADP-ribose, reaction mechanism, overview. Asp314 is essential for the formation of the binuclear metal center. A conformational switch of ARH3 enables specific substrate recognition. ARH3 specifically exposes the scissile 1''-O-linkage in substrates for cleavage
additional information
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proposed catalytic role of residue Asp314. Asp314 is located proximal to the 1''-O-linkage in substrates. Asp314 might protonate the leaving group (general acid), forming an oxocarbenium ion intermediate, and then activate the water (general base) for back-side attack. The W1 ligand of MgB can serve as the nucleophile attacking the anomeric C1'' of the ribose''. This is consistent with the observed O18 incorporation during hydrolysis of O-acetyl-ADP-ribose, reaction mechanism, overview. Asp314 is essential for the formation of the binuclear metal center. A conformational switch of ARH3 enables specific substrate recognition. ARH3 specifically exposes the scissile 1''-O-linkage in substrates for cleavage
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
additional information
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CD spectra of enzyme DrPARG in the absence and presence of ADP-ribose exhibit increased proportion of alpha-helices and beta-strands from 11.78% and 30.37% to 15.10% and 33.52%, respectively, which suggests that conformational changes occur during the binding of ADP-ribose. The intrinsically disordered N-terminal region of DrPARG might be highly flexible. ADP-ribose binding pocket and complex structure, and conformational effects, detailed overview
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additional information
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CD spectra of enzyme DrPARG in the absence and presence of ADP-ribose exhibit increased proportion of alpha-helices and beta-strands from 11.78% and 30.37% to 15.10% and 33.52%, respectively, which suggests that conformational changes occur during the binding of ADP-ribose. The intrinsically disordered N-terminal region of DrPARG might be highly flexible. ADP-ribose binding pocket and complex structure, and conformational effects, detailed overview
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additional information
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CD spectra of enzyme DrPARG in the absence and presence of ADP-ribose exhibit increased proportion of alpha-helices and beta-strands from 11.78% and 30.37% to 15.10% and 33.52%, respectively, which suggests that conformational changes occur during the binding of ADP-ribose. The intrinsically disordered N-terminal region of DrPARG might be highly flexible. ADP-ribose binding pocket and complex structure, and conformational effects, detailed overview
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additional information
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CD spectra of enzyme DrPARG in the absence and presence of ADP-ribose exhibit increased proportion of alpha-helices and beta-strands from 11.78% and 30.37% to 15.10% and 33.52%, respectively, which suggests that conformational changes occur during the binding of ADP-ribose. The intrinsically disordered N-terminal region of DrPARG might be highly flexible. ADP-ribose binding pocket and complex structure, and conformational effects, detailed overview
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additional information
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CD spectra of enzyme DrPARG in the absence and presence of ADP-ribose exhibit increased proportion of alpha-helices and beta-strands from 11.78% and 30.37% to 15.10% and 33.52%, respectively, which suggests that conformational changes occur during the binding of ADP-ribose. The intrinsically disordered N-terminal region of DrPARG might be highly flexible. ADP-ribose binding pocket and complex structure, and conformational effects, detailed overview
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additional information
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CD spectra of enzyme DrPARG in the absence and presence of ADP-ribose exhibit increased proportion of alpha-helices and beta-strands from 11.78% and 30.37% to 15.10% and 33.52%, respectively, which suggests that conformational changes occur during the binding of ADP-ribose. The intrinsically disordered N-terminal region of DrPARG might be highly flexible. ADP-ribose binding pocket and complex structure, and conformational effects, detailed overview
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additional information
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CD spectra of enzyme DrPARG in the absence and presence of ADP-ribose exhibit increased proportion of alpha-helices and beta-strands from 11.78% and 30.37% to 15.10% and 33.52%, respectively, which suggests that conformational changes occur during the binding of ADP-ribose. The intrinsically disordered N-terminal region of DrPARG might be highly flexible. ADP-ribose binding pocket and complex structure, and conformational effects, detailed overview
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additional information
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CD spectra of enzyme DrPARG in the absence and presence of ADP-ribose exhibit increased proportion of alpha-helices and beta-strands from 11.78% and 30.37% to 15.10% and 33.52%, respectively, which suggests that conformational changes occur during the binding of ADP-ribose. The intrinsically disordered N-terminal region of DrPARG might be highly flexible. ADP-ribose binding pocket and complex structure, and conformational effects, detailed overview
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