Synergy between SIRT1 and SIRT6 helps recognize DNA breaks and potentiates the DNA damage response and repair in humans and mice
Synergy between SIRT1 and SIRT6 helps recognize DNA breaks and potentiates the DNA damage response and repair in humans and mice
复制标题
SIRT1 和 SIRT6 之间的协同作用有助于识别 DNA 断裂并增强人类和小鼠的 DNA 损伤反应和修复
DOI：
10.7554/elife.55828
复制
发表时间：
2020-06-15
期刊：
影响因子：
7.7
通讯作者：
Liu, Baohua
中科院分区：
文献类型：
--
作者：
Meng, Fanbiao;Qian, Minxian;Liu, Baohua
DNA损伤反应（DDR）是一个高度协调的过程，但双链DNA断裂（DSB）最初是如何识别的尚不清楚。在这里，我们表明，聚合SIRT 6脱乙酰酶识别DSB和增强DDR在人类和小鼠细胞。首先，SIRT 1在残基K33处使SIRT 6脱乙酰基，这对于SIRT 6聚合和向DSB移动是重要的。然后，K33-脱乙酰化的SIRT 6锚定到γ H2 AX，允许其保留在局部染色质上并随后重塑。我们发现，一个K33 R突变，模仿hypoacetylated SIRT 6可以挽救有缺陷的DNA修复，由于SIRT 1缺陷培养细胞。这些数据突出了SIRT在人类和小鼠中DDR和DNA修复的时空调节中的协同作用。
The DNA damage response (DDR) is a highly orchestrated process but how double-strand DNA breaks (DSBs) are initially recognized is unclear. Here, we show that polymerized SIRT6 deacetylase recognizes DSBs and potentiates the DDR in human and mouse cells. First, SIRT1 deacetylates SIRT6 at residue K33, which is important for SIRT6 polymerization and mobilization toward DSBs. Then, K33-deacetylated SIRT6 anchors to gamma H2AX, allowing its retention on and subsequent remodeling of local chromatin. We show that a K33R mutation that mimics hypoacetylated SIRT6 can rescue defective DNA repair as a result of SIRT1 deficiency in cultured cells. These data highlight the synergistic action between SIRTs in the spatiotemporal regulation of the DDR and DNA repair in humans and mice.