Suppression of G1 arrest and enhancement of G2 arrest by inhibitors of poly(ADP-ribose) polymerase: possible involvement of poly(ADP-ribosyl)ation in cell cycle arrest following gamma-irradiation.
Low-dose gamma-irradiation of mouse embryonic fibroblast C3D2F1 3T3-a cells caused G1 arrest along with G2 arrest and inhibition of replicative DNA synthesis. When the cells were cultured in the presence of inhibitors of poly(ADP-ribose) polymerase [EC 2.4.2.30], such as 3-aminobenzamide, benzamide and luminol, G1 arrest of C3D2F1 3T3-a cells was suppressed and enhancement of G2 arrest was observed. In contrast, 3-aminobenzoic acid, a non-inhibitory analog of 3-aminobenzamide, did not suppress G1 arrest following gamma-irradiation. These results suggest that the poly(ADP-ribosyl)ation reaction is critical for the pathway of G1 arrest and is also involved in the pathway of G2 arrest.
Nozaki
T
T
Biochemistry Division, National Cancer Center Research Institute, Tokyo.
Masutani
M
M
Akagawa
T
T
Sugimura
T
T
Esumi
H
H
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002460:Cell Line; D004249:DNA Damage; D004260:DNA Repair; D016193:G1 Phase / Q000187:drug effects / Q000528:radiation effects*; D016195:G2 Phase / Q000187:drug effects / Q000528:radiation effects*; D005720:Gamma Rays; D051379:Mice; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology*
D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C025160:3-aminobenzamide; D011065:Poly(ADP-ribose) Polymerases