Effect of Selected Octadeoxyribonucleotides and 6-Amino-1,2 Benzopyrone on Poly(ADP-Ribose) Transferase Activity

Abstract

Polymerization of ADP-ribose from NAD⁺ by poly(ADP-ribose) transferase is initiated by auto-mono-ADP-ribosylation of the enzyme followed by ADP-ribose transfer to other acceptor proteins and subsequent elongation (1). DNA is required as a coenzyme, and an enzyme-associated DNA, defined as sDNA (2), can be isolated which is more efficient than crude calf thymus DNA (3). It was reported that introduction of cleavage sites into double-stranded DNA coincides with an increased rate of poly(ADP-ribose) synthesis (4). However, only a few poly(ADP-ribosyl) transferase molecules (as located by electron microscopy) are at the ends of sDNA (2), and the existence of highly fragmented DNA does not inevitably coincide with a high rate of poly(ADP-ribosyl)ation (5). Furthermore, maximal activation of the enzyme in the nucleus may be catalyzed by “short DNA pieces” not detectable by methods which are suitable for assay of DNA fragmentation (6). We have observed that hormonal action in vivo and in cell cultures coincides with a decrease in poly(ADP-ribosyl)ation without a diminution of enzyme content (7). Since a specific interaction between hormone-receptor complexes and certain DNA sequences is well known [7], we assumed that the observed correlation between hormone action and decreased rates of poly(ADP-ribosyl)ation may suggest altered binding sites for the enzyme on DNA sequences (or structures) that are less efficient coenzymes for polyADP(ribose) transferase than the DNA sites prior to hormone action.