Phosphorylated histone H2AX foci persist on rejoined mitotic chromosomes in normal human diploid cells exposed to ionizing radiation
Phosphorylated histone H2AX foci persist on rejoined mitotic chromosomes in normal human diploid cells exposed to ionizing radiation
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DOI：
10.1667/rr3508.1
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发表时间：
2006-03-01
影响因子：
3.4
通讯作者：
Watanabe, M
中科院分区：
文献类型：
--
作者：
Suzuki, M;Suzuki, K;Watanabe, M
组蛋白H2AX被磷酸化并响应于暴露于电离辐射而形成病灶。人们一直认为，磷酸化组蛋白H2AX焦点反映未修复的DNA双链断裂，然而，我们在这里报告的本地化磷酸化组蛋白H2AX焦点在重新连接的DNA双链断裂的网站。我们观察到，磷酸化组蛋白H2AX焦点仍然存在，甚至96小时后，暴露于X射线在间期细胞。为了澄清残留的磷酸化组蛋白H2AX焦点的定位，我们研究了X射线照射的有丝分裂染色体上焦点形成的定位。我们发现磷酸化的组蛋白H2AX焦点不仅位于染色体片段上，而且位于没有片段的完整中期染色体上。在分裂后期细胞中，由于DNA断裂末端的不合法重新连接而形成的染色体桥具有磷酸化的组蛋白H2AX灶。这些病灶在X射线照射后30 min检测为单个小斑点，但在X射线照射后20或96 h检测到的病灶沿着染色体桥聚集。这些结果表明，如果DNA断裂重新连接，磷酸化组蛋白H2AX焦点持续存在。有人建议，“残余”灶表明异常的染色质结构的非法重新加入，而不是DNA双链断裂本身。(C)2006年，辐射研究协会。
Histone H2AX is phosphorylated and forms foci in response to exposure to ionizing radiation. It has been thought that phosphorylated histone H2AX foci reflect unrepaired DNA double-strand breaks; however, we report here the localization of phosphorylated histone H2AX foci at the site of rejoined DNA double-strand breaks. We observed that phosphorylated histone H2AX foci remained even 96 h after exposure to X rays in interphase cells. To clarify the localization of residual phosphorylated histone H2AX foci, we examined localization of focus formation on mitotic chromosomes irradiated with X rays. We found that phosphorylated histone H2AX foci were located not only on chromosomal fragments but also on intact metaphase chromosomes without fragments. In anaphase cells, chromosomal bridges, which resulted from illegitimate rejoining of DNA broken ends, had phosphorylated histone H2AX foci. These foci were detected as individual small spots 30 min after X irradiation, but foci detected 20 or 96 h after X irradiation were clustered along the chromosomal bridges. These results indicate that phosphorylated histone H2AX foci persist if DNA breaks are rejoined. It is suggested that "residual" foci indicate an aberrant chromatin structure by illegitimate rejoining but not a DNA double-strand break itself. (C) 2006 by Radiation Research Society.