PARP3

PARP3 (poly(ADP-ribose) polymerase 3) is a mono-ADP-ribosyltransferase that contributes to genome integrity by participating in cellular responses to DNA damage and by supporting mitotic progression^[1][2]. Mechanistically, PARP3 is recruited to DNA double-strand breaks (DSBs) and functions within the classical non-homologous end joining (c-NHEJ) pathway, where it cooperates with DNA repair factors including APLF, Ku70, and Ku80 to promote efficient DNA end joining^[1][3]. PARP3 also facilitates retention of DNA ligation machinery at damaged chromatin and accelerates repair of chromosomal DSBs, linking ADP-ribosylation signaling to repair pathway execution^[3][4]. In experimental models, depletion or genetic loss of PARP3 delays DSB repair, reduces accurate NHEJ activity, and alters the balance between homologous recombination (HR) and NHEJ repair mechanisms^[3][4]. Mechanistically, PARP3 interacts with and ADP-ribosylates Ku70/Ku80, limiting DNA end resection and thereby influencing repair pathway choice after DNA damage^[4]. Disease-relevant studies further indicate that PARP3 contributes to genome stability and cellular resistance to DNA-damaging agents, supporting its importance in cancer-associated DNA repair networks^[4][5]. Compared with the related isoforms PARP1 and PARP2, PARP3 exhibits distinct biological functions, responds to different DNA break structures, and remains functionally nonredundant in several DNA repair contexts despite partial cooperation with other nuclear PARP family members^[5]. For experimental applications, PARP3 possesses a druggable catalytic domain, making it a useful target for mechanistic studies of DNA repair pathway regulation and genome maintenance^[5].