We think this paper is highly cited because it represents the first comprehensive picture of an emerging family of enzymes so far depicted only by its founding member: poly(ADP-ribose) polymerase-1 (PARP-1), a key-enzyme involved in the detection, signaling, and resolution of DNA strand-breaks associated with cell metabolism or induced by environmental genotoxins. Given the enormous interest of the pharmaceutical industry in the development of PARP-1 inhibitors that have recently entered clinical trials in cancer therapy and inflammatory diseases, it presents an overview of all the family members in terms of both structure and function.

The recent sequencing of the human genome as well as the availability of enormous quantities of short expressed sequences (ESTs) presented the opportunity to find out if other PARP-containing sequences existed in the human. Although the methodology used in this paper was not new, the unexpected size of this superfamily was. Extensive use of bioinformatics-based analysis of the human genome led us to discover and describe 10 new proteins in addition to the seven already known PARP members to complete the 17-member PARP family. The interesting feature of these new proteins is that they contain, in addition to their common PARP domain, a large variety of new functional modules which are linked to various potential functions in mammalian cells.

The size of the PARP superfamily (17 members in total ) opens new opportunities in the field as these proteins can be categorized according to their domain structure into functional subfamilies that could potentially interest the scientific community as well as industry.

Our initial observations made in 1983 together with Dr. Guy Poirier (Laval University) concerning the implication of PARP activity during DNA damage and chromatin repair laid the basis for our incessant interest in the biology of PARPs. The various and fascinating facets of PARP activity in both cell survival and cell death may explain the apparent disappointment of the scientific community, which for a while, considered PARP-1 as only an accessory factor in the single-strand break repair (SSBR) pathway. The integrated approach developed by our team, along with the enormous effort of the PARP research community to unravel the physiological role of this activity has now largely paid off by the satisfaction of seeing the new PARP inhibitors going from the bench to bedside.