PARG His tag Protein, Mouse

PARG (Poly(ADP-ribose) Glycohydrolase) serves as the key negative regulator of PAR metabolism, belonging to the glycoside hydrolase family that modulates protein PARylation levels through hydrolysis of glycosidic bonds within PAR chains. Structurally, PARG comprises an N-terminal regulatory domain and a C-terminal catalytic domain; the catalytic domain forms an α/β-barrel fold with an active site constituted by a catalytic triad of Glu755/Glu756/Asp737, executing exoglycosidase activity by binding to terminal ADP-ribose units of PAR chains, with His-tags commonly employed for recombinant protein purification. Functionally, PARG maintains dynamic equilibrium with PARPs (particularly PARP1/2) to rapidly degrade PAR chains and preserve cellular PARylation homeostasis, thereby regulating DNA damage repair, replication fork restart, transcriptional control, and cell death; PARG deficiency leads to PAR chain accumulation, triggering replication stress and genomic instability. Clinically, PARG inhibitors (such as COH34 and PDD00017273) exhibit synthetic lethality with PARP inhibitors, demonstrating therapeutic potential for BRCA-mutant tumors and PARP inhibitor-resistant patients, currently positioned at preclinical/early clinical development stages as an emerging target for synthetic lethal strategies.