PARP Activation and Necrotic Cell Death

Poly(ADP-ribose) polymerase (PARP) protein family consists of at least 17 members. They catalyze the chemical reaction termed polyADP-ribosylation, which functions to cleave nicotinamide adenine dinucleotide into ADP-ribose and nicotinamide mononucleotide (NAM), and transfer ADP-ribose to glutamate, aspartate, or lysine residues on substrate proteins to form poly(ADP-ribosyl)ated chains. PARP proteins play an essential role in chromatin organization, DNA repair, replication, and transcriptional regulation. Upon excessive DNA damage, PARP is hyperactivated and causes cell death. This chapter summarizes the molecular regulation of cell death by PARP.