Biosynthesis and Degradation of Poly(ADP-Ribose) Synthetase

Abstract

Poly(ADP-ribose) synthetase is a chromatin-bound enzyme which produces a protein bound homopolymer of ADP-ribose using NAD as a substrate (1). The enzyme from calf thymus has been purified to homogeneity and extensively characterized in several laboratories (2–4). Using limited proteolysis, we recently demonstrated that the enzyme (Mr = 120,000) consists of three functionally different domains, the first (Mr = 46,000) for binding of DNA, the second (Mr = 22,000) for accepting poly(ADP-ribose) and the third (Mr = 54,000) for binding of the substrate, NAD (5, 6). We also demonstrated by immunoblotting that endogenous degradation products of the enzyme were present in calf thymus (7–9). Nevertheless, detailed processes of synthesis and degradation of this enzyme in vivo are not as yet fully understood.