Binding of chromatin-modifying activities to phosphorylated histone H2A at DNA damage sites
Binding of chromatin-modifying activities to phosphorylated histone H2A at DNA damage sites
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DOI：
10.1016/j.molcel.2004.12.003
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发表时间：
2004-12-22
期刊：
影响因子：
16
通讯作者：
Côté, J
中科院分区：
文献类型：
--
作者：
Downs, JA;Allard, S;Côté, J
DNA 损伤后，酵母组蛋白 H2A 在 Ser129 上被磷酸化，这是有效修复所需的事件。我们发现磷酸化在 DNA 双链断裂 (DSB) 周围的大范围内快速发生。组蛋白 H4 乙酰化对于 DSB 修复也很重要，我们发现 NuA4 HAT 复合物与磷酸化 H2A 肽特异性结合。单个 NuA4 亚基 Arp4 负责相互作用。 NuA4 复合物随着 H2A P-Ser129 的出现而被招募到 DSB，而 Arp4 对于这种结合很重要。 Arp4 也是 Ino80 和 Swr1 染色质重塑复合物的一个亚基，也与 H2A P-Ser129 相互作用并被招募到 DSB。该关联再次需要 Arp4，但也需要之前的 NuA4 招募和行动。因此，H2A 在 DNA 损伤位点的磷酸化会产生可被不同染色质修饰剂识别的标记。这种相互作用导致染色质逐步重新配置，从而实现有效的 DNA 修复。
Yeast histone H2A is phosphorylated on Ser129 upon DNA damage, an event required for efficient repair. We show that phosphorylation occurs rapidly over a large region around DNA double-strand breaks (DSBs). Histone H4 acetylation is also important for DSB repair, and we found that the NuA4 HAT complex associates specifically with phospho-H2A peptides. A single NuA4 subunit, Arp4, is responsible for the interaction. The NuA4 complex is recruited to a DSB concomitantly with the appearance of H2A P-Ser129 and Arp4 is important for this binding. Arp4 is also a subunit of the Ino80 and Swr1 chromatin remodeling complexes, which also interact with H2A P-Ser129 and are recruited to DSBs. This association again requires Arp4 but also prior NuA4 recruitment and action. Thus, phosphorylation of H2A at DNA damage sites creates a mark recognized by different chromatin modifiers. This interaction leads to stepwise chromatin reconfiguration, allowing efficient DNA repair.