PARG

Poly(ADP-ribose) glycohydrolase (PARG) is the major enzyme responsible for the catabolism of poly(ADP-ribose), a reversible covalent-modifier of chromosomal proteins. The protein is found in many tissues and may be subject to proteolysis generating smaller, active products. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2015]

Full Name

Poly(ADP-Ribose) Glycohydrolase

Function

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:34321462, PubMed:34019811).
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).

Biological Process

ATP generation from poly-ADP-D-riboseManual Assertion Based On ExperimentIDA:UniProtKB
Base-excision repair, gap-fillingTAS:Reactome
Carbohydrate metabolic processIEA:InterPro
Nucleotide-sugar metabolic processManual Assertion Based On ExperimentIBA:GO_Central
Regulation of DNA repairManual Assertion Based On ExperimentIBA:GO_Central
Regulation of histone modificationManual Assertion Based On ExperimentIBA:GO_Central

Cellular Location

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