Studies of nuclear ADP-ribosylation

Recent studies on poly(ADP-ribose) are reviewed. Poly(ADP-ribose) was shown to have α(1″ → 2′) ribose-ribose bonds. High molecular weight poly(ADP-ribose) with a branched structure was demonstrated. The structure of the branch linkage was determined as 2″-[1′-ribosyl-2″ (1‴-ribosyl)]-adenosine 5′,5″,5‴-tris(phosphate). The known sites of ADP-ribosylation of proteins were summarized. The enzymatic synthesis of poly(ADP-ribose) was classified into three steps, initiation, elongation and branching. Degradation of poly(ADP-ribose) may be mainly performed by α(1″ → 2′)-poly(ADP-ribose) ribohydrolase. Specific antibodies against poly(ADP-ribose) and its monomer, 2′-ribosyl adenosine 5′,5″-bis(phosphate), were obtained and used for quantitative measurement of naturally occurring poly(ADP-ribose). High antibody activity was found in the serum of the patients with systemic lupus erythematosus. Poly(A)·poly(U) could also raise specific antibody against poly(ADP-ribose) in rabbits. Nicotinamide, an inhibitor of poly(ADP-ribose) polymerase, increased sister chromatid exchanges. Among the nicotinamide analogues tested, N′-methylnicotinamide was the best inducer of differentiation of Friend erythroleukemia cells. Purified poly(ADP-ribose) induced differentiation of mouse myelogenous leukemia cells.