(ADP-ribose)n Participates in DNA Excision Repair

Nature. 1980 Feb 7;283(5747):593-6. doi: 10.1038/283593a0.

Abstract

Chromatin proteins are covalently modified by at least five different processes; in no case has the precise physiological function been established. One of these post-synthetic, covalent modifications is effected by the enzyme poly(ADP-ribose) polymerase, which uses the coenzyme NAD+ to ADP-ribosylate chromatin proteins. The modification consists largely of mono(ADP-ribose), but long, homopolymer chains of (ADP-ribose) are also present. Various physiological functions have been suggested for (ADP-ribose)n. Here we demonstrate that one function of (ADP-ribose)n is to participate in the cellular recovery from DNA damage. Specific inhibitors of poly(ADP-ribose) polymerase prevent rejoining of DNA strand breaks caused by dimethyl sulphate and cytotoxicity is enhanced thereby. The rejoining of strand breaks is prevented also by nutritionally depleting the cells of NAD.

MeSH terms

  • ADP Ribose Transferases*
  • Alkylating Agents / pharmacology
  • Animals
  • Benzamides / pharmacology
  • DNA Repair* / drug effects
  • Leukemia L1210
  • Mice
  • NAD / metabolism*
  • NAD+ Nucleosidase / metabolism*
  • Nucleoside Diphosphate Sugars / metabolism*
  • Poly Adenosine Diphosphate Ribose / metabolism*
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly(ADP-ribose) Polymerases / metabolism*

Substances

  • Alkylating Agents
  • Benzamides
  • Nucleoside Diphosphate Sugars
  • Poly(ADP-ribose) Polymerase Inhibitors
  • NAD
  • Poly Adenosine Diphosphate Ribose
  • ADP Ribose Transferases
  • Poly(ADP-ribose) Polymerases
  • NAD+ Nucleosidase