PARG

PARG, or poly(ADP-ribose) glycohydrolase, is an enzyme that reverses the action of poly(ADP-ribose) polymerases (PARPs) by degrading poly(ADP-ribose) (PAR) chains attached to proteins. In response to DNA damage, PARP enzymes catalyze the addition of PAR units to nuclear and cytoplasmic targets to recruit DNA repair factors. PARG hydrolyzes the glycosidic bonds within these PAR polymers, shortening or removing PAR chains and helping terminate PAR signaling and restore normal cellular function.

In humans, the PARG gene encodes multiple protein isoforms produced by alternative splicing and promoter usage, resulting in nuclear and cytoplasmic localizations. PARG expression is widespread and can be induced by DNA damage and oxidative stress, reflecting its role in the DNA damage response and chromatin dynamics.

Biologically, PARG activity is essential for proper DNA repair and chromatin remodeling. Because it regulates PAR turnover, PARG influences cell survival after genotoxic stress. The accumulation of PAR can be cytotoxic, which has spurred interest in pharmacological inhibition of PARG as a potential anticancer strategy. PARG inhibitors may enhance the efficacy of PARP inhibitors or sensitize tumor cells to DNA-damaging therapy, while in other contexts they can promote PAR- and NAD+-dependent cell death.

PARG is conserved across eukaryotes, and related enzymes have been identified in various organisms. Ongoing research aims to clarify its precise roles in DNA repair, chromatin dynamics, and stress responses, and to evaluate its potential as a therapeutic target.