Role of poly(ADP-ribose) polymerase in cell-cycle checkpoint mechanisms following gamma-irradiation

Biochimie. 1995;77(6):462-5. doi: 10.1016/0300-9084(96)88161-2.

Abstract

A nuclear poly(ADP-ribose) polymerase (PARP) is activated by gamma-irradiation and consequently synthesizes poly(ADP-ribose) by binding to DNA strand-breaks. This property suggests that PARP is a DNA strand-break-signal generator. Meanwhile, the cell-cycle arrest occurs in G1 and G2 phases following gamma-irradiation. We found that PARP inhibitors including 3-aminobenzamide (3-AB) suppressed G1 arrest and enhanced G2 arrest following gamma-irradiation. These observations suggested that PARP is critical for the induction of G1 arrest and is also involved in the regulation of G2 arrest. Furthermore, the effects of 3-AB on the G1-arrest signal-transduction pathway were also studied. We found that p53 stabilization following gamma-irradiation was not inhibited but the p53-responsive transient increases of WAF1/CIP1/p21 and MDM-2 mRNA were suppressed by 3-AB. Therefore, it is suggested that PARP participates in G1-arrest signal-transduction pathway through the modulation of WAF1/CIP1/p21 and MDM-2 mRNA expression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • DNA Damage*
  • Enzyme Activation
  • G1 Phase / drug effects
  • G1 Phase / radiation effects*
  • G2 Phase / radiation effects*
  • Gamma Rays
  • Humans
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly(ADP-ribose) Polymerases / physiology*
  • Poly(ADP-ribose) Polymerases / radiation effects
  • Radiation-Sensitizing Agents / pharmacology
  • Signal Transduction / drug effects

Substances

  • Poly(ADP-ribose) Polymerase Inhibitors
  • Radiation-Sensitizing Agents
  • Poly(ADP-ribose) Polymerases