Poly(ADP-ribose) polymerase 1 (PARP1, also known as ADPRT1) is a multifunctional human ADP-ribosyltransferase. It plays a key role in multiple DNA repair pathways, such as base excision repair (BER), non-homologous end joining (NHEJ), homologous recombination (HR), and Okazaki-fragment processing pathways. In response to DNA strand breaks, PARP1 covalently attaches ADP-ribose moieties to itself and other proteins, recruiting DNA repair proteins to the damage site [2].

PARP1-deficient cells exhibit phenotypes related to replication stress and genome integrity. For example, inactivation of UFL1, which is essential for UFMylation of PARP1 at K548 during replication stress, leads to similar phenotypes as seen in PARP1-deficient cells, including delayed CHK1 activation and inhibited nascent DNA degradation during replication blockage. A PARP1 UFMylation-deficient mutant (K548R) and pathogenic mutant (F553L) compromise CHK1 activation, the restart of stalled replication forks, and chromosome stability [1]. Also, PARP1 UFMylation-deficient knock-in mice show increased sensitivity to replication stress from anticancer treatments [1].

In conclusion, PARP1 is crucial for DNA repair and maintaining genome integrity. Studies using PARP1-related genetic models, such as UFMylation-deficient mutants and knock-in mice, have revealed its role in replication stress response and cancer-related processes. These findings contribute to understanding the mechanisms of diseases and developing targeted therapies, especially in cancers where PARP1-targeted therapy is being explored [1,2].