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Literature summary for 3.2.1.143 extracted from

  • Gravells, P.; Grant, E.; Smith, K.M.; James, D.I.; Bryant, H.E.
    Specific killing of DNA damage-response deficient cells with inhibitors of poly(ADP-ribose) glycohydrolase (2017), DNA Repair, 52, 81-91 .
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
drug development single treatment therapy with PARG inhibitors can be used for treatment of certain homologous recombination-deficient tumours Homo sapiens
molecular biology specific killing of DNA damage-response deficient cells with inhibitors of poly(ADP-ribose) glycohydrolase Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
gene PARG, real-time PCR expression analysis Homo sapiens

Protein Variants

Protein Variants Comment Organism
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 Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
additional information specific killing of DNA damage-response deficient cells with inhibitors of poly(ADP-ribose) glycohydrolase. Single treatment therapy with PARG inhibitors can be used for treatment of certain homologous recombination-deficient tumours and provide insight into the relationship between poly(ADP-ribose) polymerase (PARP), PARG and the processes of DNA repair Homo sapiens
PDD00017273
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Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens Q86W56
-
-

Source Tissue

Source Tissue Comment Organism Textmining
breast adenocarcinoma cell
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Homo sapiens
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MCF-7 cell
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Homo sapiens
-

Synonyms

Synonyms Comment Organism
PARG
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Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.0000026
-
pH and temperature not specified in the publication Homo sapiens PDD00017273

General Information

General Information Comment Organism
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 Homo sapiens
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 Homo sapiens