title: Interstitial chromatin alteration causes persistent p53 activation involved in the radiation-induced senescence-like growth arrest.
abstract: Various stresses including ionizing radiation give normal human fibroblasts a phenotype of senescence-like growth arrest (SLGA), manifested by p53-dependent irreversible G1 arrest. To determine the mechanism of persistent activation of p53, we examined phosphorylated Ataxia telangiectasia mutated (ATM) and phosphorylated histone H2AX foci formation after X-irradiation. Although the multiple tiny foci, detected soon after (<30 min) irradiation, gradually disappeared, some of these foci changed to large foci and persisted for 5 days. Large foci containing phosphorylated ATM and gamma-H2AX co-localized and foci with p53 phosphorylated at serine 15 also showed the same distribution. Interestingly, the signals obtained by telomere fluorescence in situ hybridization (FISH) assay did not co-localize with 90% of the large foci. Our results indicate that chromatin alteration in interstitial chromosomal regions is the most likely cause of continuous activation of p53, which results in the induction of SLGA by ionizing radiation.
authors.affiliation: Division of Radiation Biology, Department of Radiology and Radiation Biology, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Suzuki
authors.forename: Keiji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Seiji
authors.initials: S
authors.lastname: Kodama
authors.forename: Masami
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D002453:Cell Cycle / Q000528:radiation effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology* / Q000528:radiation effects*; D002843:Chromatin / Q000235:genetics* / Q000528:radiation effects*; D002869:Chromosome Aberrations / Q000528:radiation effects; D004171:Diploidy; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000378:metabolism* / Q000528:radiation effects*; D006801:Humans; D011829:Radiation Dosage; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*
chemical_list: D002843:Chromatin; D016159:Tumor Suppressor Protein p53