PARP1 (poly(ADP-ribose) polymerase 1) is a nuclear DNA damage sensor that catalyzes the synthesis of poly(ADP-ribose) (PAR) chains from NAD+ upon binding to DNA breaks and non-B DNA structures 1. The enzyme functions through co-condensation with DNA at double-strand break sites, exerting mechanical forces to maintain DNA end synapsis and becoming enzymatically active for PAR synthesis 2. PARP1 also associates with R-loops to promote their resolution and prevent genomic instability 3. Beyond DNA repair, PARP1 interacts with chr1 regulatory complexes like WDR5 to facilitate target gene recognition and transcriptional regulation 4. In cell death pathways, PARP1 plays dual roles: excessive PAR production leads to parthanatos, a caspase-independent programmed cell death 5, while caspase cleavage of PARP1 generates an 89-kDa fragment that serves as a cytoplasmic PAR carrier, facilitating AIF-mediated apoptosis 6. PARP1 also regulates mitochondrial homeostasis through interactions with POLG and UCP2, affecting mitochondrial DNA synthesis and oxidative phosphorylation 7. The protein's regulation involves E3 ubiquitin ligases like RNF114, which target PARP1 for degradation to prevent excessive trapping at DNA lesions 8.