Oxidative Stress Diverts tRNA Synthetase to Nucleus for Protection against DNA Damage
| Autor: | Kathleen M. Fisch, Na Wei, Xiang-Lei Yang, Yun-Shiuan Olivia Hsu, Andrew I. Su, Tao Xu, Elisabeth Gardiner, Shuji Kishi, Xiaohua Wu, Guangsen Fu, Yi Shi, Lan N. Truong |
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| Rok vydání: | 2014 |
| Předmět: |
DNA Repair
DNA damage DNA repair Active Transport Cell Nucleus RAD51 Repressor Histone Deacetylase 1 Tripartite Motif-Containing Protein 28 Biology Hydroxamic Acids Article Morpholinos Tyrosine-tRNA Ligase Cell Line Tumor Protein biosynthesis Animals Humans E2F1 DNA Breaks Double-Stranded Molecular Biology Zebrafish Cell Nucleus BRCA1 Protein E2F1 Transcription Factor Ribonuclease Pancreatic Cell Biology Protein Structure Tertiary Up-Regulation Cell biology Enzyme Activation Histone Deacetylase Inhibitors Repressor Proteins Oxidative Stress Cytosol HEK293 Cells Biochemistry Rad51 Recombinase DNA Damage HeLa Cells |
| Zdroj: | Molecular Cell. 56:323-332 |
| ISSN: | 1097-2765 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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