title: ADP-ribosylation of diadenosine 5',5"-P1,P4-tetraphosphate by poly(ADP-ribose) polymerase in vitro.
abstract: When the effect of diadenosine 5',5"'-P1,P4-tetraphosphate on a purified poly(ADP-ribose) polymerase reaction was examined, the compound strongly inhibited ADP-ribosylation reaction of histone, while the compound was much less inhibitory of the Mg2+-dependent automodification of this enzyme. In an attempt to study the mechanism of the inhibition, we analyzed the total reaction products, which were synthesized from NAD+ in the presence of diadenosine 5',5"'-P1,P4-tetraphosphate in a reaction mixture for ADP-ribosylation of histone, and found that a new, low molecular product was predominantly synthesized instead of ADP-ribosylated histone in the reaction. Approximately 90% of added NAD+ was converted into this low molecular product under an appropriate reaction condition. Further analysis revealed that the product was mono- and oligo(ADP-ribosyl)ated diadenosine nucleotide and that the bound oligo(ADP-ribose) is elongating at one end of the product during the reaction. Thus, the present study clearly demonstrated that diadenosine 5',5"'-P1,P4-tetraphosphate functions as an acceptor for ADP-ribose in a poly(ADP-ribose) polymerase reaction in vitro. The finding that histone H1 is required in the reaction mixture for the synthesis of this new product suggests that histone H1 and the diadenosine compound interact during this modification reaction.
mesh_terms: D000227:Adenine Nucleotides / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D015226:Dinucleoside Phosphates; D006657:Histones / Q000378:metabolism; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D009244:NAD+ Nucleosidase / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D013950:Thymus Gland / Q000201:enzymology*
chemical_list: D000227:Adenine Nucleotides; D015226:Dinucleoside Phosphates; D006657:Histones; C020733:diadenosine tetraphosphate; D011065:Poly(ADP-ribose) Polymerases; D009244:NAD+ Nucleosidase; D008274:Magnesium