Environmental Stress and the Regulation of Poly(ADP-Ribose) Metabolism

Abstract

The nuclear metabolism of poly(ADP-ribose) involves at least three enzymatic activities, poly(ADP-ribose) polymerase, poly(ADP-ribose) glycohydrolase, and protein-mono(ADP-ribose) lyase. Although each of these enzymes has been purified and studied, we still have a poor understanding of poly(ADP-ribose) metabolism and its regulation in intact cells. Two features of poly(ADP-ribose) metabolism in intact cells are illustrated in Fig. 1. First, the occurrence of environmentally-induced DNA damage results in a rapid elevation of the intracellular levels of polymer. Current evidence from both in vitro and in vivo studies argues that this alteration is regulated at the level of poly(ADP-ribose) polymerase and that the activating factor is the appearance of DNA strand breaks [1, 2]. A second feature is that polymers are rapidly turning over in vitro. This indicates that individual polymers are required only transiently to fulfill their function or that the coordinated synthesis and degradation of the polymer results in a longer term change in chromatin structure.