Interstitial chromatin alteration causes persistent p53 activation involved in the radiation-induced senescence-like growth arrest
Interstitial chromatin alteration causes persistent p53 activation involved in the radiation-induced senescence-like growth arrest
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DOI：
10.1016/j.bbrc.2005.11.167
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发表时间：
2006-02-03
影响因子：
3.1
通讯作者：
Watanabe, M
中科院分区：
文献类型：
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作者：
Suzuki, M;Suzuki, K;Watanabe, M
包括电离辐射在内的各种应力使正常人成纤维细胞出现衰老样生长停滞（SLGA）表型，表现为p53依赖性不可逆G1期阻滞。为了确定p53持续激活的机制，我们研究了X射线照射后磷酸化共济失调毛细血管扩张突变（ATM）和磷酸化组蛋白H2 AX灶的形成。虽然在照射后不久（< 30分钟）检测到的多个小病灶逐渐消失，但其中一些病灶变为大病灶并持续5天。含有磷酸化ATM和γ-H2 AX共定位的大病灶和p53在丝氨酸15处磷酸化的病灶也显示出相同的分布。有趣的是，通过端粒荧光原位杂交（FISH）测定获得的信号没有与90%的大病灶共定位。我们的研究结果表明，染色质改变间质染色体区域是最有可能的原因连续激活p53，这导致在SLGA的诱导电离辐射。(c)2005年爱思唯尔公司All rights reserved.
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. (c) 2005 Elsevier Inc. All rights reserved.