polyADPribose

Poly(ADP-ribose) (PAR), sometimes written polyADP-ribose, is a negatively charged polymer of repeating ADP-ribose units formed by PARPs in response to DNA damage, using NAD+ as substrate. PAR can be covalently attached to proteins (PARylation) or exist as free polymers that participate in nuclear signaling.

PAR chains vary in length and can be branched. Major synthetic enzymes include PARP1, PARP2 and PARP3; tankyrases contribute in specific pathways. Degradation is mainly by PARG, with ARH3 removing ribose–ribose bonds. PARP activity is modulated by HPF1, which helps target serine residues on proteins.

Biological roles include chromatin relaxation and recruitment of DNA repair factors at damage sites, stabilization of replication forks, and regulation of transcription and metabolism. PAR signaling relies on reader proteins that recognize PAR. Excess PAR synthesis can deplete NAD+ and ATP, contributing to parthanatos, a form of cell death involving AIF.

Clinical relevance: PARP inhibitors such as olaparib, niraparib, rucaparib and talazoparib exploit synthetic lethality in BRCA1/2- or HR-defective tumors by trapping PARP on DNA and inhibiting repair. PAR and PARP activity are also studied as biomarkers of DNA damage response and inflammation; dysregulation has been linked to ischemia, neurodegeneration and aging in some contexts.

Measurement and research: PAR can be detected by antibodies, mass spectrometry, or enzymatic assays. Reader domains and motifs mediate PAR signaling, translating it into cellular responses. The balance of PAR synthesis and degradation shapes the DNA damage response and cell fate decisions.