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 cellul ar reaction to DNA strand breakage as induced by alkylating agents, ionizin g radiation or oxidants. The resulting formation of protein-coupled poly(AD P-ribose) facilitates survival of proliferating cells under conditions of D NA damage, probably via its contribution to DNA base-excision repair. Furth ermore, based on recent results there is a role emerging for PARP-1 as a ne gative regulator of genomic instability in cells under genotoxic stress. Re garding 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 promisin g strategies to improve the outcome of such therapy, albeit for different r easons. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.