DNA damage-dependent acetylation and ubiquitination of H2AX enhances chromatin dynamics
DNA damage-dependent acetylation and ubiquitination of H2AX enhances chromatin dynamics
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DOI：
10.1128/mcb.00579-07
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发表时间：
2007-10-01
影响因子：
5.3
通讯作者：
Kamiya, Kenji
中科院分区：
文献类型：
--
作者：
Ikura, Tsuyoshi;Tashiro, Satoshi;Kamiya, Kenji
染色质重组在DNA修复、细胞凋亡和细胞周期检查点中起重要作用。在参与染色质重组的蛋白质中，TIP 60组蛋白乙酰转移酶已被证明在DNA修复和凋亡中发挥作用。然而，TIP 60如何调节人类细胞对DNA损伤的反应中的染色质重组在很大程度上是未知的。在这里，我们表明，电离辐射诱导TIP 60乙酰化组蛋白H2 AX，一种变异形式的H2 A已知的DNA损伤后磷酸化。此外，TIP 60通过泛素缀合酶UBC 13调节H2 AX的泛素化，这是由DNA损伤诱导的。H2 AX的这种泛素化需要其预先乙酰化。我们还证明了TIP 60-UBC 13复合物的乙酰化依赖性泛素化导致H2 AX从受损的染色质中释放。我们的结论是，顺序乙酰化和泛素化H2 AX的TIP 60-UBC 13促进增强组蛋白动力学，这反过来又刺激DNA损伤反应。
Chromatin reorganization plays an important role in DNA repair, apoptosis, and cell cycle checkpoints. Among proteins involved in chromatin reorganization, TIP60 histone acetyltransferase has been shown to play a role in DNA repair and apoptosis. However, how TIP60 regulates chromatin reorganization in the response of human cells to DNA damage is largely unknown. Here, we show that ionizing irradiation induces TIP60 acetylation of histone H2AX, a variant form of H2A known to be phosphorylated following DNA damage. Furthermore, TIP60 regulates the ubiquitination of H2AX via the ubiquitin-conjugating enzyme UBC13, which is induced by DNA damage. This ubiquitination of H2AX requires its prior acetylation. We also demonstrate that acetylation-dependent ubiquitination by the TIP60-UBC13 complex leads to the release of H2AX from damaged chromatin. We conclude that the sequential acetylation and ubiquitination of H2AX by TIP60-UBC13 promote enhanced histone dynamics, which in turn stimulate a DNA damage response.