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
  • Tyrosine-tRNA Ligase/biosynthesis
  • Tyrosine-tRNA Ligase/genetics
  • Tyrosine-tRNA Ligase/metabolism*
  • HeLa Cells
  • DNA Damage/genetics*
  • Histone Deacetylase 1/antagonists & inhibitors
  • Histone Deacetylase 1/metabolism
  • Ribonuclease, Pancreatic/metabolism
  • Hydroxamic Acids/pharmacology
  • Up-Regulation
  • Animals
  • Oxidative Stress/genetics*
  • Cell Nucleus/genetics
  • Cell Nucleus/metabolism*
  • Zebrafish
  • DNA Breaks, Double-Stranded
  • BRCA1 Protein/biosynthesis
  • Humans
  • Morpholinos/genetics
  • DNA Repair/genetics*
  • Rad51 Recombinase/biosynthesis
  • Enzyme Activation
  • Active Transport, Cell Nucleus/genetics
  • Repressor Proteins/metabolism
  • Cell Line, Tumor
  • Protein Structure, Tertiary
  • Histone Deacetylase Inhibitors/pharmacology
  • E2F1 Transcription Factor/metabolism
PubMed
25284223 Full text @ Mol. Cell
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.
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