title: Poly(ADP-ribose) polymerase inhibits DNA synthesis initiation in the absence of NAD.
abstract: Poly(ADP-ribose) polymerase (ADPRP) is a nuclear enzyme that transfers ADP-ribose from NAD+ to diverse nuclear proteins. Previously, the function of ADPRP was considered to relate exclusively to its catalytic activity. However, recent experiments have shown that ADPRP is actually an abundant DNA-binding protein, and that the potential catalytic activity of the enzyme is more than 100-fold greater than the measured rates of NAD+ turnover in intact cells. To better understand the role of ADPRP, we have used highly purified ADPRP and a monospecific autoantibody to examine the effects of ADPRP on in vitro DNA synthesis in the presence or absence of NAD+ substrate. The data show that DNA synthesis initiation is blocked by ADPRP and that auto-poly (ADP-ribosyl)ation reverses the process by diminishing the DNA binding capacity of the protein. These results suggest that ADPRP actually is a structural DNA binding protein, whose catalytic activity serves to modulate its interaction with DNA.
authors.affiliation: Department of Molecular and Experimental Medicine, Scripps Clinic and Research Foundation, La Jolla, California 92037.
authors.forename: T
authors.initials: T
authors.lastname: Nobori
authors.forename: H
authors.initials: H
authors.lastname: Yamanaka
authors.forename: D A
authors.initials: DA
authors.lastname: Carson
mesh_terms: D000818:Animals; D002417:Cattle; D004247:DNA / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D009243:NAD / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*
chemical_list: D009243:NAD; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases