3.2.1.143: poly(ADP-ribose) glycohydrolase
This is an abbreviated version!
For detailed information about poly(ADP-ribose) glycohydrolase, go to the full flat file.
Word Map on EC 3.2.1.143
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3.2.1.143
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polyadp-ribose
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polyadp-ribosylation
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parp-1
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polymerase-1
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adp-ribosylation
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genotoxic
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parylation
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gallotannins
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analysis
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drug development
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parthanatos
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automodification
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adp-ribosylhydrolase
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pharmacology
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padpr
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olaparib
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molecular biology
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aif
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medicine
- 3.2.1.143
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polyadp-ribose
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polyadp-ribosylation
- parp-1
- polymerase-1
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adp-ribosylation
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genotoxic
-
parylation
- gallotannins
- analysis
- drug development
-
parthanatos
-
automodification
-
adp-ribosylhydrolase
- pharmacology
-
padpr
- olaparib
- molecular biology
- aif
- medicine
Reaction
Synonyms
ADP-ribose glycohydrolase, ADP-ribosyl-acceptor hydrolase 3, ADPRHL2, ARH3, DrPARG, FOXG_05947, Genbank AB019366-derived protein GI 6518480, Genbank U78975-derived protein GI 2062407, glycohydrolase, poly(adenosine diphosphoribose), glycohydrolase, poly(adenosine diphosphoribose) (cattle clone 4/5), glycohydrolase, poly(adenosine diphosphoribose) (Rattus norvegicus strain BUF gene Parg), PAR glycohydrolase, PAR glycohydrolase, PARG, PARG1, PARG110, PARG111, PARG59, poly (ADP-ribose) glycohydrolase, poly(adenosine diphosphoribose) glycohydrolase, poly(adenosine diphosphoribose) glycosidase, poly(ADP-ribose) glycohydrolase, poly(ADP-ribose) glycohydrolase (Arabidopsis thaliana gene At2g31860), poly(ADP-ribose) glycohydrolase (Arabidopsis thaliana gene At2g31870), poly(ADP-ribose) glycohydrolase (cattly clone 4/5), poly(ADP-ribose) glycohydrolase 1, poly(ADP-ribose)glycohydrolase, poly(ADP-ribosyl) glycohydrolase, poly-ADP-glycohydrolase
ECTree
3.2.1.143 poly(ADP-ribose) glycohydrolaseAdvanced search results
results (
results (Engineering
Engineering on EC 3.2.1.143 - poly(ADP-ribose) glycohydrolase
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
E273N
E756N
T267K
site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
T267R
site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
T267K
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site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
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T267R
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site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
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T267K
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site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
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T267R
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site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
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T267K
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site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
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T267R
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site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
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T267K
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site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
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T267R
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site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
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T267K
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site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
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T267R
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site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
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T267K
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site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
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T267R
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site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
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T267K
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site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
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T267R
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site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
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T267K
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site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
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T267R
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site-directed mutagenesis, the mutant loses its endoglycohydrolase activity but retains the exo activity on poly(ADP-ribose), PAR
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D314A
site-directed mutagenesis, the mutation impairs ARH3-dependent DNA damage repair
D314E
site-directed mutagenesis, poly(ADP-ribose) binding structures of wild-type and D314A mutant, overview
D77N
site-directed mutagenesis, the mutation impairs ARH3-dependent DNA damage repair
E41Q
site-directed mutagenesis, the mutation impairs ARH3-dependent DNA damage repair
H182A
site-directed mutagenesis, the mutation impairs ARH3-dependent DNA damage repair
K616A/Q617A/K618A/E688A/K689A/K690A
site-directed mutagenesis, six surface entropy reduction mutations
L11D/L13D/L14D
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the mutant results in no detectable activity (less than 0.1% activity)
S148A
site-directed mutagenesis, the mutation impairs ARH3-dependent DNA damage repair
T317A
site-directed mutagenesis, the mutation impairs ARH3-dependent DNA damage repair
Y149A
site-directed mutagenesis, the mutation impairs ARH3-dependent DNA damage repair
D77N/D78N
no enzymic activity, binding of ADP-ribose is similar to wild-type
E748N
site-directed mutagenesis, the mutant is inactive, activity is disrupted due to significant conformational changes
E748Q
site-directed mutagenesis, the mutant activity is highly reduced compared to the wild-type enzyme
E749N
site-directed mutagenesis, the mutant is inactive, activity is disrupted due to significant conformational changes
E749Q
site-directed mutagenesis, the mutant activity is highly reduced compared to the wild-type enzyme
F868A
site-directed mutagenesis, the mutant activity is reduced compared to the wild-type enzyme
G737A/G738A
site-directed mutagenesis, the mutant activity is reduced compared to the wild-type enzyme
G866A
site-directed mutagenesis, the mutant activity is reduced compared to the wild-type enzyme
E114A
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the mutant shows about 2% activity compared to the wild type enzyme
S298K
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the mutant shows about 2% activity compared to the wild type enzyme
V226W
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the mutant shows about 5% activity compared to the wild type enzyme
additional information
additional information
enzyme knock-down by RNAi results in increased radiation sensitivity of worms
additional information
enzyme knock-down by RNAi results in increased radiation sensitivity of worms
additional information
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enzyme knock-down by RNAi results in increased radiation sensitivity of worms
additional information
disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. A substitution of Arg268 for the smaller and uncharged side chain of Thr267 than that of arginine disrupts the interaction matrix of Thr267, Asp260, and n ribose' and allows for accommodating the n+1 ADP-ribose
additional information
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disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. A substitution of Arg268 for the smaller and uncharged side chain of Thr267 than that of arginine disrupts the interaction matrix of Thr267, Asp260, and n ribose' and allows for accommodating the n+1 ADP-ribose
additional information
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disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. A substitution of Arg268 for the smaller and uncharged side chain of Thr267 than that of arginine disrupts the interaction matrix of Thr267, Asp260, and n ribose' and allows for accommodating the n+1 ADP-ribose
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additional information
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disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. A substitution of Arg268 for the smaller and uncharged side chain of Thr267 than that of arginine disrupts the interaction matrix of Thr267, Asp260, and n ribose' and allows for accommodating the n+1 ADP-ribose
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additional information
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disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. A substitution of Arg268 for the smaller and uncharged side chain of Thr267 than that of arginine disrupts the interaction matrix of Thr267, Asp260, and n ribose' and allows for accommodating the n+1 ADP-ribose
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additional information
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disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. A substitution of Arg268 for the smaller and uncharged side chain of Thr267 than that of arginine disrupts the interaction matrix of Thr267, Asp260, and n ribose' and allows for accommodating the n+1 ADP-ribose
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additional information
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disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. A substitution of Arg268 for the smaller and uncharged side chain of Thr267 than that of arginine disrupts the interaction matrix of Thr267, Asp260, and n ribose' and allows for accommodating the n+1 ADP-ribose
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additional information
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disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. A substitution of Arg268 for the smaller and uncharged side chain of Thr267 than that of arginine disrupts the interaction matrix of Thr267, Asp260, and n ribose' and allows for accommodating the n+1 ADP-ribose
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additional information
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disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. A substitution of Arg268 for the smaller and uncharged side chain of Thr267 than that of arginine disrupts the interaction matrix of Thr267, Asp260, and n ribose' and allows for accommodating the n+1 ADP-ribose
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additional information
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disruption of DrPARG expression causes accumulation of endogenous poly-ADP-ribose (PAR) and compromises recovery from UV radiation damage. A substitution of Arg268 for the smaller and uncharged side chain of Thr267 than that of arginine disrupts the interaction matrix of Thr267, Asp260, and n ribose' and allows for accommodating the n+1 ADP-ribose
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additional information
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decrease or loss of enzyme expression by partial gene deletion or RNA results in mislocalization and hypermodification of silencing protein SIR2
additional information
construction of a DELTAparg deletion mutant. The mutant DELTAparg strain, in the presence of H2O2, exhibits a reduced randomly amplified polymorphic DNA (RAPD) pattern, suggesting that DNA is damaged in this strain and repair is impaired
additional information
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construction of a DELTAparg deletion mutant. The mutant DELTAparg strain, in the presence of H2O2, exhibits a reduced randomly amplified polymorphic DNA (RAPD) pattern, suggesting that DNA is damaged in this strain and repair is impaired
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additional information
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construction of a DELTAparg deletion mutant. The mutant DELTAparg strain, in the presence of H2O2, exhibits a reduced randomly amplified polymorphic DNA (RAPD) pattern, suggesting that DNA is damaged in this strain and repair is impaired
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additional information
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construction of a DELTAparg deletion mutant. The mutant DELTAparg strain, in the presence of H2O2, exhibits a reduced randomly amplified polymorphic DNA (RAPD) pattern, suggesting that DNA is damaged in this strain and repair is impaired
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additional information
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construction of a DELTAparg deletion mutant. The mutant DELTAparg strain, in the presence of H2O2, exhibits a reduced randomly amplified polymorphic DNA (RAPD) pattern, suggesting that DNA is damaged in this strain and repair is impaired
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additional information
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quantification of single-strand break repair rates in A-549 cells depleted of poly(ADP-ribose) glycohydrolase, poly(ADP-ribose) polymerase 1 and poly(ADP-ribose) polymerase 2, both separately and in combination. Poly(ADP-ribose) glycohydrolase is a critical component of single-strand break repair and accelerates this process in concert with poly(ADP-ribose) polymerase
additional information
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transient transfection of HeLa cells with PARG expression constructs with amino acids encoded by exon 4 at the N-terminus. Proteins are targeted to the mitochondria. Deletion and missense mutants allow identification of a canonical N-terminal mitochondrial targeting sequence consisting of the first 16 amino acids encoded by PARG exon 4. Sub-mitochondrial localization experiments indicate that this mitochondrial PARG isoform is targeted to the mitochondrial matrix
additional information
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deletion of the regulatory segment/MTS from full-length human PARG111 results in a complete loss of activity
additional information
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constitutive expression shRNA directed against the catalytic domain of all enzyme isoforms in the 16HBE cell line
additional information
lentiviral gene silencing is used to generate 16HBE cell lines with stably suppressed enzyme, and determination of parameters of cell death and cell cycle following benz[a]pyrene exposure, overview
additional information
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lentiviral gene silencing is used to generate 16HBE cell lines with stably suppressed enzyme, and determination of parameters of cell death and cell cycle following benz[a]pyrene exposure, overview
additional information
enzyme knockout by expression of ARH3 siRNA in U2OS cells
additional information
poly(ADP-ribose) glycohydrolase (PARG) silencing and generation of PARG-deficient human bronchial epithelial cells. Silencing of PARG significantly reduces the volume and weight of tumors in Balb/c nude mice injected with benzo(a)pyrene (BaP)-induced transformed human bronchial epithelial cells. PARG-silenced shPARG cells show less chromosomal damage than wild-type 16HBE cells. PARG silencing inhibits BaP-induced micronuclei formation. PARG silencing protects cells against BaP-induced cytotoxicity and cytogenetic damage, and inhibits BaP-induced cell transformation by reducing genomic instability in cells. PARG-deficient phenotype, overview
additional information
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poly(ADP-ribose) glycohydrolase (PARG) silencing and generation of PARG-deficient human bronchial epithelial cells. Silencing of PARG significantly reduces the volume and weight of tumors in Balb/c nude mice injected with benzo(a)pyrene (BaP)-induced transformed human bronchial epithelial cells. PARG-silenced shPARG cells show less chromosomal damage than wild-type 16HBE cells. PARG silencing inhibits BaP-induced micronuclei formation. PARG silencing protects cells against BaP-induced cytotoxicity and cytogenetic damage, and inhibits BaP-induced cell transformation by reducing genomic instability in cells. PARG-deficient phenotype, overview
additional information
siRNA screen for synthetic lethality with PARG depletion, lethal with depletion of BRCA2. Reduction of expression of PARG protein by 80-90% without significant change in poly(ADP-ribose) polymerase PARP1 protein levels. Disruption of BRCA1, BRCA2, PALB2, RAD51D, BRIP1, BARD1, MRE11, NBN, RAD50, TP53, and FAM175A can be considered synthetically lethal with PARG depletion
additional information
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deletion of enzyme gene by gene targeting in embryonic stem cells and mice, severe compromisation of automodification of poly(ADP-ribose) polymerase 1. Enzyme deficient mice are viable and fertile, but hypersensitive to alkylating agents and ionizing radiation, and susceptible to streptozotocin-induced diabetes and endotoxic shock
additional information
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enzyme knockout mutation is lethal. Silencing by RNA interference results in 10% of enzyme protein that are sufficient to ensure normal proliferation through several subculturing rounds and cells that are able to repair DNA damage induced by sublethal doses of H2O2. Silenced cells are more resistant than wild-type to oxidant-induced apoptosis while exhibiting delayed poly(ADP-ribose) degradation and transient accumulation of ADP-ribose polymers
additional information
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disruption of poly(ADP-ribose) glycohydrolase gene results in significant reduction of spinal cord inflammation and tissue injury, neutrophil infiltration, cytokine production, and apoptosis upon spinal cord injury
additional information
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hypomorphic mouse model in which exons 2 and 3 of PARG gene have been deleted. Mutants exhibits nuclear localization of the enzyme which contains a catalytic domain but lacks the N-terminal region. Following DNA damage induced by N-methyl-N'-nitro-N-nitrosoguanidine, activity of both poly(ADP-ribose) glycohydrolase and poly(ADP-ribose) polymerase in mutant cell increases. Increase in poly(ADP-ribose) glycohydrolase activity leads to decrease in poly(ADP-ribose) polymerase-1 automodification resulting in increased activity. Mutant cells also show reduced formation of XCRR1 foci, delayed H2AX phosphorylation, decreased DNA break intermediates during repair, and increased cell death
additional information
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mice lacking the functional 110 kDa isoform of enzyme are resistant to colon injury by dinitrobenzene sulfonic acid. Mucosa of mutant mice colon tissue shows reduction of myeloperoxidase activity and attenuated staining for intercellular adhesion molecule 1 and vascular cell adhesion molecule 1. Overproduction of proinflammatory factors tumor necrosis factor alpha and interleukin 1beta and activation of cell death signaling pathway are inhibited in these mice
additional information
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the catalytic activity of poly(ADP-ribose) glucohydrolase strongly depends on the two Glu residues in the GGG-X6-8-QEE motif (E114 and E115)
