H2AX phosphorylation within the G1 phase after UV irradiation depends on nucleotide excision repair and not DNA double-strand breaks
H2AX phosphorylation within the G1 phase after UV irradiation depends on nucleotide excision repair and not DNA double-strand breaks
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DOI：
10.1073/pnas.0603779103
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发表时间：
2006-06-27
影响因子：
11.1
通讯作者：
Cleaver, James E.
中科院分区：
文献类型：
--
作者：
Marti, Thomas M.;Hefner, Eli;Cleaver, James E.
变异组蛋白H2AX以复杂的方式响应原代人成纤维细胞的紫外线照射而被磷酸化，这与DNA双链断裂后通常报道的含量完全不同。暴露于电离辐射后的H2AX磷酸化会产生灶，可通过免疫荧光显微镜检测到，并已被用作DNA双链断裂的清晰且一致的定量标记。在这里，我们表明，与电离辐射相反，紫外线辐射主要诱导H2AX磷酸化作为弥漫性，甚至是泛核染色。紫外线诱导的H2AX的泛核磷酸化存在于细胞周期的所有阶段，在S期最高。 G中的H2AX磷酸化，细胞取决于可能将S-139位点暴露于激酶活性的核苷酸切除修复因子，不是由于DNA双链断裂，并且在UV诱导的信号转导中起着比先前所实现的更大的作用。
The variant histone H2AX is phosphorylated in response to UV irradiation of primary human fibroblasts in a complex fashion that is radically different from that commonly reported after DNA double-strand breaks. H2AX phosphorylation after exposure to ionizing radiation produces foci, which are detectable by immunofluorescence microscopy and have been adopted as clear and consistent quantitative markers for DNA double-strand breaks. Here we show that in contrast to ionizing radiation, UV irradiation mainly induces H2AX phosphorylation as a diffuse, even, pan-nuclear staining. UV induced pan-nuclear phosphorylation of H2AX is present in all phases of the cell cycle and is highest in S phase. H2AX phosphorylation in G, cells depends on nucleotide excision repair factors that may expose the S-139 site to kinase activity, is not due to DNA double-strand breaks, and plays a larger role in UV-induced signal transduction than previously realized.