PUBLICATION
Oxidative Stress Diverts tRNA Synthetase to Nucleus for Protection against DNA Damage
- Authors
- Wei, N., Shi, Y., Truong, L.N., Fisch, K.M., Xu, T., Gardiner, E., Fu, G., Hsu, Y.S., Kishi, S., Su, A.I., Wu, X., Yang, X.L.
- ID
- ZDB-PUB-141007-4
- Date
- 2014
- Source
- Molecular Cell 56(2): 323-32 (Journal)
- Registered Authors
- Kishi, Shuji
- Keywords
- none
- MeSH Terms
-
- HEK293 Cells
- E2F1 Transcription Factor/metabolism
- HeLa Cells
- Hydroxamic Acids/pharmacology
- Histone Deacetylase 1/antagonists & inhibitors
- Histone Deacetylase 1/metabolism
- DNA Repair/genetics*
- DNA Breaks, Double-Stranded
- Cell Nucleus/genetics
- Cell Nucleus/metabolism*
- Cell Line, Tumor
- Oxidative Stress/genetics*
- Histone Deacetylase Inhibitors/pharmacology
- Morpholinos/genetics
- Protein Structure, Tertiary
- BRCA1 Protein/biosynthesis
- Ribonuclease, Pancreatic/metabolism
- DNA Damage/genetics*
- Zebrafish
- Up-Regulation
- Humans
- Repressor Proteins/metabolism
- Animals
- Enzyme Activation
- Tyrosine-tRNA Ligase/biosynthesis
- Tyrosine-tRNA Ligase/genetics
- Tyrosine-tRNA Ligase/metabolism*
- Rad51 Recombinase/biosynthesis
- Active Transport, Cell Nucleus/genetics
- PubMed
- 25284223 Full text @ Mol. Cell
Citation
Wei, N., Shi, Y., Truong, L.N., Fisch, K.M., Xu, T., Gardiner, E., Fu, G., Hsu, Y.S., Kishi, S., Su, A.I., Wu, X., Yang, X.L. (2014) Oxidative Stress Diverts tRNA Synthetase to Nucleus for Protection against DNA Damage. Molecular Cell. 56(2):323-32.
Abstract
Tyrosyl-tRNA synthetase (TyrRS) is known for its essential aminoacylation function in protein synthesis. Here we report a function for TyrRS in DNA damage protection. We found that oxidative stress, which often downregulates 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 upregulate 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 repressor and its associated HDAC1 from deacetylating and suppressing E2F1. Remarkably, overexpression of TyrRS strongly protects against UV-induced DNA double-strand breaks in zebrafish, whereas 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping