In the 80’s, the multifunctional and modular nature of PARP was established, and the enzyme has been shown to bind to DNA structures containing either nicks, gaps, cruciforms, and DNA bent structures.

With the cloning of the human PARP cDNA in 1987 started the era of molecular biology and molecular genetics of poly (ADP-ribosyl)ation reactions. Overexpression of cloned PARP cDNAs in various expression systems provided new tools to investigate the modular organization of the enzyme in three functional domains. Easy purification of large amounts of recombinant chicken PARP catalytic fragment led to the X-ray determination of its structure, both in the absence and in the presence of various inhibitors.

The generation of PARP deficient mice by several laboratories has engaged the study of poly(ADP-ribosyl)ation reactions in a vastly wider field than was previously appreciated. The caretaker functions of PARP have been totally confirmed using these animal models. Unexpectedly, the knockout strategy has revealed the instrumental role of this enzyme in necrotic cell death after ischemia-reperfusion injury and in various inflammatory process.

The first evidence that structurally different PARP proteins may possess DNA-dependent poly (ADP-ribose) activities came in 1995 with the discovery of a gene coding for a PARP-related polypeptide APP in Arabidopsis thaliana. Since then, many other proteins with PARP activity have been identified in mammals, leading to a new family of proteins : the PARP family.

This rapidly-growing PARP family leads the scientists to now explore the connections between DNA damage and DNA repair with cancer, ageing, autoimmune disease, cerebrovascular disease, and coronary artery disease. Since members of the family are actors in the genome surveillance, we would not be surprised that considerable interest for the PARP’s is going to bring us, all together, to significant breakthroughs in understanding cancer development, and, may be more futuristic, in the life span of humans.