Poly(ADP-ribose) polymerase inhibits DNA synthesis initiation in the absence of NAD.
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.
Nobori
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Department of Molecular and Experimental Medicine, Scripps Clinic and Research Foundation, La Jolla, California 92037.
Yamanaka
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H
Carson
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DA
D000818:Animals; D002417:Cattle; D004247:DNA / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D009243:NAD / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*
D009243:NAD; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases