Poly (ADP-Ribose) Glycohydrolase-Dependent dePARylation of PCNA Is Essential for DNA Replication.

ABSTRACT: Poly (ADP-ribosyl)ation (PARylation) plays a crucial role in DNA replication, particularly during S phase, where it is detected at replication sites on the lagging strand to facilitate Okazaki fragment processing. However, the role of dePARylation in DNA replication remains elusive. In this study, we demonstrate that poly (ADP-ribose) glycohydrolase (PARG) is actively involved in degrading poly (ADP-ribose) at DNA replication sites during S phase. Inhibition of PARG in S-phase cells leads to the accumulation of DNA single-strand breaks at replication sites. Furthermore, suppression of dePARylation during S phase impairs DNA replication, which can be rescued by wild-type PARG but not by a catalytically inactive PARG mutant. Mechanistically, we show that PCNA, a key factor in DNA replication

SUBMITTER: Yan Z 

PROVIDER: S-EPMC12363383 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature