Poly(ADP-ribose) glycohydrolase

The PIP-box mediates interaction with PCNA and localization to replication foci.

Poly(ADP-ribose) glycohydrolase that degrades poly(ADP-ribose) by hydrolyzing the ribose-ribose bonds present in poly(ADP-ribose) (PubMed:15450800, PubMed:21892188, PubMed:23102699, PubMed:23474714, PubMed:33186521, PubMed:34019811, PubMed:34321462). PARG acts both as an endo- and exoglycosidase, releasing poly(ADP-ribose) of different length as well as ADP-ribose monomers (PubMed:23102699, PubMed:23481255). It is however unable to cleave the ester bond between the terminal ADP-ribose and ADP-ribosylated residues, leaving proteins that are mono-ADP-ribosylated (PubMed:21892188, PubMed:23474714, PubMed:33186521). Poly(ADP-ribose) is synthesized after DNA damage is only present transiently and is rapidly degraded by PARG (PubMed:23102699, PubMed:34019811). Required to prevent detrimental accumulation of poly(ADP-ribose) upon prolonged replicative stress, while it is not required for recovery from transient replicative stress (PubMed:24906880). Responsible for the prevalence of mono-ADP-ribosylated proteins in cells, thanks to its ability to degrade poly(ADP-ribose) without cleaving the terminal protein-ribose bond (PubMed:33186521). Required for retinoid acid-dependent gene transactivation, probably by removing poly(ADP-ribose) from histone demethylase KDM4D, allowing chromatin derepression at RAR-dependent gene promoters (PubMed:23102699). Involved in the synthesis of ATP in the nucleus, together with PARP1, NMNAT1 and NUDT5 (PubMed:27257257). Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming (PubMed:27257257).

Belongs to the poly(ADP-ribose) glycohydrolase family.

Ubiquitously expressed.

• Isoform 1
• Nucleus
• Colocalizes with PCNA at replication foci (PubMed:21398629). Relocalizes to the cytoplasm in response to DNA damage (PubMed:16460818).
• Isoform 2
• Cytoplasm
• Translocates to the nucleus in response to DNA damage.
• Isoform 3
• Cytoplasm
• Isoform 4
• Cytoplasm
• Mitochondrion
• Isoform 5
• Mitochondrion matrix

Poly(ADP-ribose) glycohydrolase, PARG

• entrezGene:8505
• omim:603501
• swissprot:Q86W56

Proteins

Oncology

111110Da