Acetylated lysine 56 on histone H3 drives chromatin assembly after repair and signals for the completion of repair.

Acetylated lysine 56 on histone H3 drives chromatin assembly after repair and signals for the completion of repair.
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DOI:
10.1016/j.cell.2008.06.035
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发表时间:
2008-07-25
期刊:
影响因子:
64.5
通讯作者:
Tyler JK
Tyler JK
中科院分区:
生物学1区
文献类型:
--
作者:
Chen CC;Carson JJ;Feser J;Tamburini B;Zabaronick S;Linger J;Tyler JK

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DNA修复后染色质结构和细胞周期进程恢复的机制在很大程度上是未知的。我们发现染色质在双链断裂(DSB)修复后重新组装,这需要组蛋白伴侣Asf1。Asf1的缺失导致DSB修复后DNA损伤检查点的持续激活,这是检查点恢复缺陷的结果,导致细胞死亡。Asf1对DSB修复后染色质组装的贡献是由于其促进组蛋白乙酰转移酶Rtt109对赖氨酸56 (K56)上的游离组蛋白H3乙酰化的作用,因为模仿K56的乙酰化绕过了Asf1对染色质重组和修复后检查点恢复的要求,而阻止K56乙酰化的突变阻断了修复后染色质重组。这些结果表明,DSB修复后染色质的恢复是由乙酰化的H3 K56驱动的,这是修复完成的信号。
The mechanisms whereby chromatin structure and cell cycle progression are restored after DNA repair are largely unknown. We show that chromatin is reassembled following double-strand break (DSB) repair and that this requires the histone chaperone Asf1. Absence of Asf1 causes persistent activation of the DNA damage checkpoint after DSB repair as a consequence of defective checkpoint recovery, leading to cell death. The contribution of Asf1 towards chromatin assembly after DSB repair is due to its role in promoting acetylation of free histone H3 on lysine 56 (K56) by the histone acetyl transferase Rtt109, because mimicking acetylation of K56 bypasses the requirement for Asf1 for chromatin reassembly and checkpoint recovery after repair, while mutations that prevent K56 acetylation block chromatin reassembly after repair. These results indicate that restoration of the chromatin following DSB repair is driven by acetylated H3 K56 and that this is a signal for the completion of repair.
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