PARylated

PARylated refers to proteins that carry poly(ADP-ribose) (PAR) polymers covalently attached to them, a modification produced by poly(ADP-ribose) polymerases (PARPs). PARP1 is the primary writer of PAR chains, though several PARP family members contribute. PAR chains are synthesized from NAD+ and can be extended into long, branched polymers that alter the target protein’s charge, conformation, interactions, and localization. PARylation is often rapidly induced in response to DNA damage and can create binding platforms for downstream repair factors.

The addition and removal of PAR chains are dynamic. PARylation is reversed by enzymes such as poly(ADP-ribose) glycohydrolase (PARG) and other ADP-ribosylhydrolases, which helps restore normal cellular NAD+ levels and protein function. The modification can occur on a variety of substrates, and many PARP-mediated events are regulated by cellular stress, chromatin state, and the availability of NAD+.

Biologically, PARylation plays a central role in the DNA damage response. It promotes chromatin relaxation and serves as a recruitment scaffold for base excision repair proteins and other factors involved in DNA synthesis and ligation. It also influences transcription, replication, and sometimes cell death pathways, with excessive PARylation potentially contributing to energy depletion and necrosis.

Clinical relevance includes the use of PARP inhibitors to block PARylation in cancers with homologous recombination defects, such as BRCA1/2 mutations, exploiting synthetic lethality. PARylation levels and PARylated proteins serve as biomarkers of DNA damage response activity in research and clinical settings.

Detection of PARylated proteins is typically done with anti-PAR antibodies in techniques like Western blotting and immunofluorescence, or by proteomics approaches such as mass spectrometry.