PARG Mutation Uncovers Critical Structural Determinant for Poly(ADP-Ribose) Hydrolysis and Chromatin Regulation in Embryonic Stem Cells.

ABSTRACT: Poly(ADP-ribosyl)ation is a crucial posttranslational modification that governs gene expression, chromatin remodeling, and cellular homeostasis. This dynamic process is mediated by the opposing activities of poly(ADP-ribose) polymerases (PARPs), which synthesize poly(ADP-ribose) (pADPr), and poly(ADP-ribose) glycohydrolase (PARG), which degrades it. While PARP function has been extensively studied, the structural and mechanistic basis of PARG-mediated pADPr degradation remain incompletely understood. To investigate the role of PARG in pADPr metabolism, we employed CRISPR/Cas9-based genome editing to generate a novel Parg^29b mutant mouse embryonic stem cell (ESC) line carrying a precise deletion within the PARG catalytic domain. This deletion completely abolished pADPr hyd

SUBMITTER: Karpova Y 

PROVIDER: S-EPMC12293112 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature