Enhanced expression of the Kin17 protein immediately after low doses of ionizing radiation.
Kin17 is a mammalian nuclear protein sharing a slight sequence homology with the bacterial RecA protein. Kin17 has a zinc-finger motif and binds efficiently to curved DNA, a genomic topology associated with illegitimate recombination junctions. We investigated the relationship between the level of Kin17 protein and genomic alteration due to either impaired wild-type p53 functions or exposure to gamma rays. We used BP cells, a rodent epithelial cell system. The cell lines used were syngeneic and harbored wild-type or mutant p53 alleles and exhibited different sensitivities to gamma irradiation. In radioresistant cells (wild-type p53 genotype), the level of Kin17 protein peaked 30 min after a low dose of radiation (2 Gy), whereas maximum accumulation of p53 protein was observed 3 h postirradiation. Radiosensitive cells carrying the same mutation in both alleles of the p53 gene showed elevated basal levels of both Kin17 and p53 proteins and failed to accumulate Kin17 and p53 proteins after exposure to ionizing radiation. These cells exhibited enhanced cell death by apoptosis after gamma irradiation. Our results indicate that Kin17 protein accumulated immediately after DNA damage in cells carrying a wild-type p53 genotype, and that levels of constitutive Kin17 protein increased in highly proliferating tumorigenic cells when wild-type p53 functions were abrogated.
Biard
D S
DS
Laboratoire de Génétique de la Radiosensibilité, DSV-DRR, CEA, Fontenay aux Roses, France.
Saintigny
Y
Y
Maratrat
M
M
Paris
F
F
Martin
M
M
Angulo
J F
JF
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D001564:Benzo(a)pyrene / Q000633:toxicity; D002453:Cell Cycle / Q000528:radiation effects; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects*; D003037:Cobalt Radioisotopes; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004307:Dose-Response Relationship, Radiation; D004848:Epithelium; D005720:Gamma Rays; D015870:Gene Expression / Q000528:radiation effects*; D016158:Genes, p53 / Q000528:radiation effects; D007700:Kinetics; D008168:Lung; D009687:Nuclear Proteins; D017354:Point Mutation; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D016335:Zinc Fingers
D003037:Cobalt Radioisotopes; D004268:DNA-Binding Proteins; C489488:Kin protein, rat; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; D001564:Benzo(a)pyrene