SIRT7 is a histone desuccinylase that functionally links to chromatin compaction and genome stability.
SIRT7 is a histone desuccinylase that functionally links to chromatin compaction and genome stability.
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SIRT7 是一种组蛋白脱琥珀酰酶，其功能与染色质压缩和基因组稳定性有关。
DOI：
10.1038/ncomms12235
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发表时间：
2016-07-20
影响因子：
16.6
通讯作者：
Yu W
中科院分区：
文献类型：
--
作者：
Li L;Shi L;Yang S;Yan R;Zhang D;Yang J;He L;Li W;Yi X;Sun L;Liang J;Cheng Z;Shi L;Shang Y;Yu W
虽然SIRT7是被描述为NAD+依赖性III类组蛋白脱乙酰酶的沉默调节蛋白家族蛋白的成员，但该沉默调节蛋白的内在酶活性仍有待研究，SIRT7的细胞功能仍有待探索。在这里，我们报告，SIRT7是一个NAD+依赖性组蛋白脱琥珀酸酶。我们发现SIRT7以PARP1依赖的方式被募集到DNA双链断裂（DSB），并催化其中H3K122的去琥珀酰化，从而促进染色质凝聚和DSB修复。我们证明，SIRT7的耗竭损害DNA损伤反应过程中的染色质致密化，并使细胞对遗传毒性应激敏感。我们的研究表明SIRT7是一种组蛋白脱琥珀酸酶，为理解这种sirtuin蛋白的表观遗传调控提供了分子基础。我们的实验表明，SIRT7催化的H3K122去琥珀酰化在DNA损伤反应和细胞存活中起着关键作用，为SIRT7的细胞功能提供了一个机制性的见解。 SIRT7是被描述为NAD+依赖性III类组蛋白脱乙酰酶的沉默调节蛋白家族蛋白的成员。在这里，作者表明SIRT7是组蛋白脱琥珀酰酶，催化H3K122脱琥珀酰化，从而促进染色质浓缩和DNA双链断裂的修复。
Although SIRT7 is a member of sirtuin family proteins that are described as NAD+-dependent class III histone deacetylases, the intrinsic enzymatic activity of this sirtuin protein remains to be investigated and the cellular function of SIRT7 remains to be explored. Here we report that SIRT7 is an NAD+-dependent histone desuccinylase. We show that SIRT7 is recruited to DNA double-strand breaks (DSBs) in a PARP1-dependent manner and catalyses desuccinylation of H3K122 therein, thereby promoting chromatin condensation and DSB repair. We demonstrate that depletion of SIRT7 impairs chromatin compaction during DNA-damage response and sensitizes cells to genotoxic stresses. Our study indicates SIRT7 is a histone desuccinylase, providing a molecular basis for the understanding of epigenetic regulation by this sirtuin protein. Our experiments reveal that SIRT7-catalysed H3K122 desuccinylation is critically implemented in DNA-damage response and cell survival, providing a mechanistic insight into the cellular function of SIRT7. SIRT7 is a member of sirtuin family proteins that are described as NAD+-dependent class III histone deacetylases. Here, the authors show that SIRT7 is histone desuccinylase catalysing H3K122 desuccinylation, thereby promoting chromatin condensation and repair of DNA double strand breaks.