Oxidative stress diverts tRNA synthetase to nucleus for protection against DNA damage.
Oxidative stress diverts tRNA synthetase to nucleus for protection against DNA damage.
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DOI：
10.1016/j.molcel.2014.09.006
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发表时间：
2014-10-23
期刊：
影响因子：
16
通讯作者：
Yang, Xiang-Lei
中科院分区：
文献类型：
--
作者：
Wei, Na;Shi, Yi;Truong, Lan N.;Fisch, Kathleen M.;Xu, Tao;Gardiner, Elisabeth;Fu, Guangsen;Hsu, Yun-Shiuan Olivia;Kishi, Shuji;Su, Andrew I.;Wu, Xiaohua;Yang, Xiang-Lei
酪氨酰-tRNA合成酶（TyrRS）在蛋白质合成中具有重要的氨酰化功能。在这里，我们报告了TyrRS在DNA损伤保护中的新功能。我们发现，氧化应激，这往往下调蛋白质的合成，诱导TyrRS迅速从胞质转移到细胞核。我们还发现，血管生成素介导或加强这种应力诱导的易位。核定位的TyrRS激活转录因子E2 F1以上调DNA损伤修复基因如BRCA 1和RAD 51的表达。这种激活是通过TyrRS与TRIM 28的直接相互作用来实现的，以隔离这种脊椎动物特异性表观遗传抑制因子及其相关的HDAC 1，使其免于脱乙酰化和抑制E2 F1。值得注意的是，TyrRS的过表达强烈地保护斑马鱼免受UV诱导的DNA双链断裂，而限制TyrRS核进入则完全取消了这种保护。因此，氧化应激触发用于蛋白质合成的必需细胞质酶易位到细胞核以保护免受DNA损伤。
Tyrosyl-tRNA synthetase (TyrRS) is known for its essential aminoacylation function in protein synthesis. Here we report a new function for TyrRS in DNA damage protection. We found that oxidative stress, which often down-regulates protein synthesis, induces TyrRS to rapidly translocate from the cytosol to the nucleus. We also found that angiogenin mediates or potentiates this stress-induced translocalization. The nuclear-localized TyrRS activates transcription factor E2F1 to up-regulate the expression of DNA damage repair genes such as BRCA1 and RAD51. The activation is achieved through direct interaction of TyrRS with TRIM28 to sequester this vertebrate-specific epigenetic repressors and its associated HDAC1 from deacetylating and suppressing E2F1. Remarkably, overexpression of TyrRS strongly protects against UV-induced DNA double-strand breaks in zebrafish, while restricting TyrRS nuclear entry completely abolishes the protection. Therefore, oxidative stress triggers an essential cytoplasmic enzyme used for protein synthesis to translocate to the nucleus to protect against DNA damage.
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DOI：
10.1073/pnas.0611671104
发表时间：
2007-02-27
影响因子：
11.1
作者：
Hoeglinger, Guenter U.;Breunig, Joshua J.;Hunot, Stephane
通讯作者：
Hunot, Stephane
影响因子：
5.3
作者：
Bindra, RS;Schaffer, PJ;Glazer, PM
通讯作者：
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影响因子：
11.4
作者：
Martínez-Balbás, MA;Bauer, UM;Kouzarides, T
通讯作者：
Kouzarides, T
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影响因子：
14.9
作者：
Feng Z;Zhang J
通讯作者：
Zhang J
影响因子：
2.9
作者：
Giege, Richard
通讯作者：
Giege, Richard