Tissue-specific DNA-PK-dependent H2AX phosphorylation and γ-H2AX elimination after X-irradiation in vivo
Tissue-specific DNA-PK-dependent H2AX phosphorylation and γ-H2AX elimination after X-irradiation in vivo
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DOI：
10.1016/j.bbrc.2008.08.095
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发表时间：
2008-11-07
影响因子：
3.1
通讯作者：
Koike, Aki
中科院分区：
文献类型：
--
作者：
Koike, Manabu;Sugasawa, Jun;Koike, Aki
响应 DNA 双链断裂，组蛋白 H2AX 在 Ser139 (gamma-H2AX) 处快速磷酸化。尽管ATM激酶和DNA-PK在培养细胞中磷酸化H2AX的Ser139，但体内γ-H2AX水平的调节机制仍不清楚。在这里，我们检测了 X 射线照射后小鼠皮肤中 H2AX 的磷酸化和 γ-H2AX 的消除。此外，在 X 射线照射后，缺乏 ATM 或 DNA-PK 的小鼠中 γ-H2AX 的水平也有所增加。尽管在这些突变小鼠的皮肤中检测到 X 辐射后的消除，但 DNA-PK 缺陷小鼠的消除速度比 C3H 和 ATM 敲除小鼠慢，表明皮肤中一部分 γ-H2AX 以 DNA-PK 依赖性方式消除。尽管在肝脏、肾脏和脾脏中也检测到了 DNA-PK 依赖性的 γ-H2AX 消除，但仅在脾脏中检测到了 DNA-PK 依赖性的 H2AX 磷酸化。这些结果表明γ-H2AX水平的调节机制是组织特异性的。 (C) 2008 Elsevier Inc. 保留所有权利。
Histone H2AX rapidly undergoes phosphorylation at Ser139 (gamma-H2AX) in response to DNA double-strand breaks. Although ATM kinase and DNA-PK phosphorylate Ser139 of H2AX in culture cells, the regulatory mechanism of gamma-H2AX level remains unclear in vivo. Here, we detected the phosphorylation of H2AX and the elimination of gamma-H2AX in the mouse skin after X-irradiation. Furthermore, following X-irradiation, the level of gamma-H2AX also increased in mice lacking either ATM or DNA-PK. Although the elimination after X-irradiation was detected in the skin of these mutant mice, the elimination in DNA-PK-deficient mice was slower than that in C3H and ATM knockout mice, suggesting that a fraction of gamma-H2AX in the skin is eliminated in a DNA-PK-dependent manner. Although the DNA-PK-dependent elimination of gamma-H2AX was also detected in the liver, kidney, and spleen, the DNA-PK-dependent phosphorylation of H2AX was detected in the spleen only. These results suggest that the regulatory mechanism of gamma-H2AX level is tissue-specific. (C) 2008 Elsevier Inc. All rights reserved.