Poly(APD-ribosyl)ation, a DNA damage-driven protein modification and regulator of genomic instability

Activation of poly(ADP-ribose) polymerase-1 (PARP-1) is an immediate cellular reaction to DNA strand breakage as induced by alkylating agents, ionizing radiation or oxidants. The resulting formation of protein-coupled poly(ADP-ribose) facilitates survival of proliferating cells under conditions of DNA damage, probably via its contribution to DNA base-excision repair. Furthermore, based on recent results there is a role emerging for PARP-1 as a negative regulator of genomic instability in cells under genotoxic stress. Regarding possible applications for clinical cancer therapy with DNA-damaging agents, it appears that both inhibition and up-regulation of the poly(ADP-ribosyl)ation response in the malignant cells to be eradicated are promising strategies to improve the outcome of such therapy, albeit for different reasons. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.