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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:
 [1];  [2];  [1];  [3];  [4]
  1. Division of Radiation Biology, Department of Radiology and Radiation Biology, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521 (Japan)
  2. (Japan)
  3. Division of Radiation Biology and Health Science, Research Institute for Advanced Science and Technology, Osaka Prefecture University, 1-2 Gakuen-cho, Sakai, Osaka 599-8570 (Japan)
  4. Laboratory of Radiation Biology, Research Reactor Institute, Kyoto University, 2-1010 Asashironishi, Kumatori-cho, Sennan-gun, Osaka 590-0494 (Japan). E-mail: nabe@rri.kyoto-u.ac.jp
Publication Date:
OSTI Identifier:
20798778
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 340; Journal Issue: 1; Other Information: DOI: 10.1016/j.bbrc.2005.11.167; PII: S0006-291X(05)02693-8; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS; BIOLOGICAL RADIATION EFFECTS; BIOLOGICAL STRESS; CHROMATIN; FIBROBLASTS; FLUORESCENCE; GROWTH; IN-SITU HYBRIDIZATION; IONIZING RADIATIONS; IRRADIATION; PHENOTYPE; SERINE

Citation Formats

Suzuki, Masatoshi, Laboratory of Radiation Biology, Research Reactor Institute, Kyoto University, 2-1010 Asashironishi, Kumatori-cho, Sennan-gun, Osaka 590-0494, Suzuki, Keiji, Kodama, Seiji, and Watanabe, Masami. Interstitial chromatin alteration causes persistent p53 activation involved in the radiation-induced senescence-like growth arrest. United States: N. p., 2006. Web. doi:10.1016/j.bbrc.2005.11.167.
Suzuki, Masatoshi, Laboratory of Radiation Biology, Research Reactor Institute, Kyoto University, 2-1010 Asashironishi, Kumatori-cho, Sennan-gun, Osaka 590-0494, Suzuki, Keiji, Kodama, Seiji, & Watanabe, Masami. Interstitial chromatin alteration causes persistent p53 activation involved in the radiation-induced senescence-like growth arrest. United States. doi:10.1016/j.bbrc.2005.11.167.
Suzuki, Masatoshi, Laboratory of Radiation Biology, Research Reactor Institute, Kyoto University, 2-1010 Asashironishi, Kumatori-cho, Sennan-gun, Osaka 590-0494, Suzuki, Keiji, Kodama, Seiji, and Watanabe, Masami. Fri . "Interstitial chromatin alteration causes persistent p53 activation involved in the radiation-induced senescence-like growth arrest". United States. doi:10.1016/j.bbrc.2005.11.167.
@article{osti_20798778,
title = {Interstitial chromatin alteration causes persistent p53 activation involved in the radiation-induced senescence-like growth arrest},
author = {Suzuki, Masatoshi and Laboratory of Radiation Biology, Research Reactor Institute, Kyoto University, 2-1010 Asashironishi, Kumatori-cho, Sennan-gun, Osaka 590-0494 and Suzuki, Keiji and Kodama, Seiji and Watanabe, Masami},
abstractNote = {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.},
doi = {10.1016/j.bbrc.2005.11.167},
journal = {Biochemical and Biophysical Research Communications},
number = 1,
volume = 340,
place = {United States},
year = {Fri Feb 03 00:00:00 EST 2006},
month = {Fri Feb 03 00:00:00 EST 2006}
}