Protein mono-ADP-ribosyltransferase PARP3 (PARP3)

Protein mono-ADP-ribosyltransferase PARP3 (commonly known as PARP3) is an enzyme belonging to the poly(ADP-ribose) polymerase family that catalyzes mono(ADPribosyl)ation rather than poly(ADPribosyl)ation like some other family members. It plays a key role in cellular responses to DNA damage by modifying nuclear proteins involved in chromatin structure and metabolism—most notably histone H2B—and facilitating efficient double-strand break repair via nonhomologous end joining pathways. Unlike ubiquitously expressed relatives such as PARP1/2, expression patterns for human/mouse isoforms differ across tissues and cell cycle stages; one isoform localizes primarily at centrosomes while another accumulates within nuclei. Overexpression can disrupt cell cycle progression without causing centrosome amplification. Inhibition of this enzyme has emerged as a promising strategy for cancer therapy due to its involvement in genome maintenance mechanisms essential for tumor survival under genotoxic stress conditions.

Other names

Poly(ADP-ribose) polymerase 3ARTD3 (alternative nomenclature in some literature)PARP family member 3

Drugs targeting this molecule typically act as competitive inhibitors at the nicotinamide binding site within the catalytic domain, thereby blocking its ADP-ribosylation activity required for DNA damage signaling and repair processes. Selective inhibition can be achieved by exploiting subtle differences in the active site compared to other PARPs.