Poly(ADP-ribosyl)ation as a fail-safe, transcription-independent, suicide mechanism in acutely DNA-damaged cells: a hypothesis.

Poly(ADP-ribose) polymerase (PARP, EC 2.4.2.30) is an abundant nuclear protein that is highly conserved and constitutively expressed in all higher eukaryotic cells investigated. Today, after about two decades of intensive research, we have a fairly comprehensive picture of its remarkable enzymatic functions and of its molecular structure. Its physiological role, however, remains controversial. The present hypothesis attempts to reconcile the different findings. By extending an earlier hypothesis, it is proposed that poly(ADP-ribosyl)ation is primarily a mechanism to prevent survival of mutated, possibly apoptosis-incompetent, cells after acute DNA-damage. Recent reviews on PARP may be found in [1-4].