Initiation of poly(ADP-ribosyl) histone synthesis by poly(ADP-ribose) synthetase.
Initiation of poly(ADP-ribosyl) histone synthesis was achieved in vitro using an apparently homogeneous preparation of poly(ADP-ribose) synthetase. When poly(ADP-ribose) was synthesized in the presence of DNA and increase amounts of histone H1, increasing portions (up to about 55%) of the product were found associated with the histone, judging from solubility in 5% HClO4 and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Most of the polymers were directly attached to the histone protein and not produced by elongation from pre-existing ADP-ribose; the cohesive end of poly(ADP-ribose), isolated as ribose 5-phosphate with snake venom phosphodiesterase digestion, was labeled almost quantitatively with [ribose (NMN)-14C]NAD. The poly(ADP-ribose) . histone linkage was labile in mild alkali and neutral NH2OH, suggesting that the same bond, probably ester, was formed in this system as in crude chromatin or isolated nuclei. Elongation of a histone-bound monomer into a polymer by this enzyme was previously demonstrated (Ueda, K., Kawaichi, M., Okayama, H., and Hayaishi, O. (1979) J. Biol. Chem. 254, 679-687), but initiation of ADP-ribose chains on histone has never been shown with a purified enzyme. This appeared to be due to the low concentrations of histone so far used. These findings indicated that a single enzyme catalyzes two different types of reaction, i.e. an attachment of ADP-ribose to histone and its elongation into a polymer.
D000818:Animals; D002417:Cattle; D006657:Histones / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D009244:NAD+ Nucleosidase / Q000378:metabolism*; D009698:Nucleoproteins / Q000096:biosynthesis*; D010727:Phosphoric Diester Hydrolases; D011064:Poly Adenosine Diphosphate Ribose; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D051381:Rats; D012261:Ribonucleoproteins / Q000096:biosynthesis*
D006657:Histones; D009698:Nucleoproteins; D012261:Ribonucleoproteins; D011064:Poly Adenosine Diphosphate Ribose; D011065:Poly(ADP-ribose) Polymerases; D010727:Phosphoric Diester Hydrolases; D009244:NAD+ Nucleosidase