PARP1

PARP1 (poly(ADP-ribose) polymerase 1) is a nuclear ADP-ribosyltransferase that functions as an early sensor of DNA strand breaks and catalyzes poly(ADP-ribosyl)ation to recruit DNA repair factors and coordinate chromatin remodeling at sites of genomic damage^[1][2]. Mechanistically, PARP1 is a central component of the DNA damage response and plays critical roles in single-strand break repair and base excision repair through the recruitment of repair proteins such as XRCC1 and associated repair complexes^[1][3]. Beyond local DNA repair, PARP1 contributes to genome surveillance by transmitting damage signals that influence repair pathway selection, replication stress responses, and maintenance of genomic stability^[1][4]. In disease contexts, impaired PARP1-regulated repair can promote genomic instability, whereas elevated dependence on PARP1-mediated repair is a characteristic feature of multiple cancer models, particularly tumors with homologous recombination defects^[4][5]. Compared with the related isoform PARP2, PARP1 accounts for the majority of DNA damage-induced poly(ADP-ribose) synthesis and displays distinct DNA-binding properties, including efficient recognition of single-strand DNA breaks, while PARP2 preferentially recognizes repair intermediates such as DNA gaps and flaps^[3][6]. These functional distinctions support nonredundant contributions of PARP1 and PARP2 to the spatial and temporal organization of DNA repair pathways^[3]. For experimental applications, PARP inhibitors have become widely used tools for investigating DNA damage responses and synthetic lethality, particularly in BRCA1/2-deficient tumor models, where suppression of PARP1-dependent repair enhances the accumulation of unrepaired DNA lesions and promotes selective cancer cell death^[5][7].