DePARylation is critical for S phase progression and cell survival.

Poly(ADP-ribosyl)ation is a reversible post-translational modification. Although PARG may have a protective effect against excessive PARP1 engagement, detailed knowledge of PARG's mechanism of action remains elusive. Here, we showed that PARG participates in DNA replication, especially in Okazaki fragment maturation. Moreover, PARG level is critically important for cellular sensitivity to PARG inhibition, which is a valuable biomarker for PARGi-based therapy.