PARP2

PARP2 (poly(ADP-ribose) polymerase 2) is a nuclear ADP-ribosyltransferase that catalyzes poly(ADP-ribosyl)ation in response to DNA strand breaks and functions as a key component of the cellular DNA damage response network^[1][2]. Mechanistically, PARP2 participates in base excision repair (BER) and single-strand break repair, where it cooperates with DNA repair factors to promote efficient lesion processing and genome maintenance^[3][4]. Beyond its canonical repair role, PARP2 contributes to chromatin-associated DNA damage signaling through the generation of branched poly(ADP-ribose) chains, a process that regulates APLF-dependent histone H3 removal and supports DNA double-strand break repair^[5]. Disease-associated studies further implicate PARP2 in inflammation, carcinogenesis, cancer progression, metabolic regulation, and oxidative stress responses, highlighting its broader biological relevance beyond genome surveillance^[6]. Compared with the closely related isoform PARP1, PARP2 possesses a distinct domain organization and lacks the classical N-terminal DNA-binding zinc-finger region found in PARP1, indicating partially nonredundant mechanisms of damage recognition and activation^[1][7]. Recent structural analyses further demonstrate that DNA damage-induced catalytic activation of PARP2 differs mechanistically from PARP1, supporting isoform-specific regulatory features within the PARP family^[8]. For experimental applications, PARP2 is frequently investigated using pharmacological PARP inhibitors, including niraparib, olaparib, rucaparib, talazoparib, and other PARP1/2-targeting compounds, which provide valuable tools for dissecting DNA repair pathways and therapeutic vulnerabilities associated with defective genome maintenance^[1][9].