gammaH2AX foci form preferentially in euchromatin after ionising-radiation.
gammaH2AX foci form preferentially in euchromatin after ionising-radiation.
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DOI：
10.1371/journal.pone.0001057
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发表时间：
2007-10-24
期刊：
影响因子：
3.7
通讯作者：
Tilby, Michael J.
中科院分区：
文献类型：
--
作者：
Cowell, Ian G.;Sunter, Nicola J.;Singh, Prim B.;Austin, Caroline A.;Durkacz, Barbara W.;Tilby, Michael J.
组蛋白变体组蛋白 H2A.X 占哺乳动物细胞中 H2A 补体的 25%。当细胞暴露于双链断裂 (DSB) 诱导剂（例如电离辐射）后，它会迅速磷酸化。 DSB 生成后几分钟内，H2AX 分子在 DNA 双链断裂 (DSB) 侧翼的大染色质结构域中被磷酸化；这些结构域可以通过免疫荧光显微镜观察到，被称为 γH2AX 焦点。 H2AX 磷酸化被认为具有提高细胞对 DNA 损伤的有效反应的作用。理论上的考虑表明 X 射线诱导的 DSB 基本上是随机的染色体分布，而实验证据并没有一致地表明相反的情况。然而，我们观察到 X 射线照射后，γH2AX 焦点的分布明显不均匀，而细胞核区域没有焦点。使用免疫荧光显微镜，我们发现组蛋白 H2AX 的局灶性磷酸化优先发生在 X 射线照射后基因组的常染色质区域。先前也已证明 H2AX 磷酸化发生在由紫外线辐射或暴露于羟基脲等试剂诱导的停滞复制叉上。在这项研究中，当这些染色质区室正在进行复制时，用羟基脲处理 S 期细胞会导致常染色质和异染色质中的 H2AX 有效磷酸化。这表明异染色质中 H2AX 磷酸化的阻断至少可以通过持续的 DNA 复制部分缓解。我们讨论了一些可能的机制来解释观察到的 H2AX 磷酸化模式。由于 γH2AX 被认为形成了招募或保留其他 DNA 修复和信号分子的平台，因此这些发现意味着异染色质中 DSB 的加工与常染色质区域中的 DSB 加工不同。基因组异染色质区室和常染色质区室对 DSB 的不同反应将对理解与核和染色质组织相关的 DNA 修复过程产生影响。
The histone variant histone H2A.X comprises up to 25% of the H2A complement in mammalian cells. It is rapidly phosphorylated following exposure of cells to double-strand break (DSB) inducing agents such as ionising radiation. Within minutes of DSB generation, H2AX molecules are phosphorylated in large chromatin domains flanking DNA double-strand breaks (DSBs); these domains can be observed by immunofluorescence microscopy and are termed γH2AX foci. H2AX phosphorylation is believed to have a role mounting an efficient cellular response to DNA damage. Theoretical considerations suggest an essentially random chromosomal distribution of X-ray induced DSBs, and experimental evidence does not consistently indicate otherwise. However, we observed an apparently uneven distribution of γH2AX foci following X-irradiation with regions of the nucleus devoid of foci. Using immunofluorescence microscopy, we show that focal phosphorylation of histone H2AX occurs preferentially in euchromatic regions of the genome following X-irradiation. H2AX phosphorylation has also been demonstrated previously to occur at stalled replication forks induced by UV radiation or exposure to agents such as hydroxyurea. In this study, treatment of S-phase cells with hydroxyurea lead to efficient H2AX phosphorylation in both euchromatin and heterochromatin at times when these chromatin compartments were undergoing replication. This suggests a block to H2AX phosphorylation in heterochromatin that is at least partially relieved by ongoing DNA replication. We discus a number of possible mechanisms that could account for the observed pattern of H2AX phosphorylation. Since γH2AX is regarded as forming a platform for the recruitment or retention of other DNA repair and signaling molecules, these findings imply that the processing of DSBs in heterochromatin differs from that in euchromatic regions. The differential responses of heterochromatic and euchromatic compartments of the genome to DSBs will have implications for understanding the processes of DNA repair in relation to nuclear and chromatin organization.
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影响因子：
4.8
作者：
Furuta, T;Takemura, H;Pommier, Y
通讯作者：
Pommier, Y
影响因子：
56.9
作者：
Celeste, A;Petersen, S;Nussenzweig, A
通讯作者：
Nussenzweig, A
在酵母和哺乳动物中，异染色质对 γ-H2AX 修饰具有抵抗力。
DOI：
10.1083/jcb.200612031
发表时间：
2007-07-16
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kim JA;Kruhlak M;Dotiwala F;Nussenzweig A;Haber JE
通讯作者：
Haber JE
影响因子：
5.8
作者：
Cowell, IG;Durkacz, BW;Tilby, MJ
通讯作者：
Tilby, MJ
影响因子：
11.4
作者：
Kourmouli, N;Theodoropoulos, PA;Georgatos, SD
通讯作者：
Georgatos, SD