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 (Comment) | Organism |
---|---|
gene PARG, real-time PCR expression analysis | Homo sapiens |
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 | 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 | - |
Homo sapiens |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | Q86W56 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
breast adenocarcinoma cell | - |
Homo sapiens | - |
MCF-7 cell | - |
Homo sapiens | - |
Synonyms | Comment | Organism |
---|---|---|
PARG | - |
Homo sapiens |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.0000026 | - |
pH and temperature not specified in the publication | Homo sapiens | PDD00017273 |
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 |