Inhibition of DNA polymerase alpha, DNA polymerase beta, terminal deoxynucleotidyl transferase, and DNA ligase II by poly(ADP-ribosyl)ation reaction in vitro

Biochem Biophys Res Commun. 1985 Apr 16;128(1):61-7. doi: 10.1016/0006-291x(85)91644-4.


Incubation of DNA polymerase alpha, DNA polymerase beta, terminal deoxynucleotidyl transferase, or DNA ligase II in a reconstituted poly(ADP-ribosyl)ating enzyme system markedly suppressed the activity of these enzymes. Components required for poly(ADP-ribose) synthesis including poly(ADP-ribose) polymerase, NAD+, DNA, and Mg2+ were all essential for the observed suppression. Purified poly(ADP-ribose) itself, however, was slightly inhibitory to all of these enzymes. Furthermore, the suppressed activities of DNA polymerase alpha, DNA polymerase beta, and terminal deoxynucleotidyl transferase were largely restored (3 to 4-fold stimulation was observed) by a mild alkaline treatment, a procedure known to hydrolyze alkaline-labile ester linkage between poly(ADP-ribose) and an acceptor protein. All of these results strongly suggest that the four nuclear enzymes were inhibited as a result of poly(ADP-ribosyl)ation of either the enzyme molecule itself or some regulatory proteins of these enzymes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • DNA / metabolism
  • DNA Ligases / antagonists & inhibitors*
  • DNA Nucleotidylexotransferase / antagonists & inhibitors*
  • DNA Nucleotidyltransferases / antagonists & inhibitors*
  • DNA Polymerase I / antagonists & inhibitors*
  • DNA Polymerase II / antagonists & inhibitors*
  • Hydrogen-Ion Concentration
  • Magnesium / metabolism
  • NAD / metabolism
  • Nucleoside Diphosphate Sugars / metabolism*
  • Osmolar Concentration
  • Poly Adenosine Diphosphate Ribose / metabolism*
  • Poly(ADP-ribose) Polymerases / metabolism
  • Polynucleotide Ligases / antagonists & inhibitors*


  • Nucleoside Diphosphate Sugars
  • NAD
  • Poly Adenosine Diphosphate Ribose
  • DNA
  • Poly(ADP-ribose) Polymerases
  • DNA Nucleotidyltransferases
  • DNA Nucleotidylexotransferase
  • DNA Polymerase I
  • DNA Polymerase II
  • DNA Ligases
  • Polynucleotide Ligases
  • Magnesium