ArticleProceedings of the National Academy of Sciences of the United States of America2016
p53-Dependent DNA damage response sensitive to editing-defective tRNA synthetase in zebrafish.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Depletion of tryptophanyl-tRNA synthetase and tryptophan accumulation triggers p53-dependent apoptosis.Cell death discovery · 2025Article
- A novel piperine derivative HJ-23 exhibits anti-colorectal cancer effects by activating the p53 pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Loss of Brcc3 in Zebrafish Embryos Increases Their Susceptibility to DNA Damage Stress.International journal of molecular sciences · 2024Article
- Tryptophanyl-tRNA synthetase-1 (WARS-1) depletion and high tryptophan concentration lead to genomic instability in Caenorhabditis elegans.Cell death discovery · 2024Article
- Mammalian mitochondrial translation infidelity leads to oxidative stress-induced cell cycle arrest and cardiomyopathy.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- High expression of VARS promotes the growth of multiple myeloma cells by causing imbalance in valine metabolism.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023Article
- Recessive aminoacyl-tRNA synthetase disorders: lessons learned fromFrontiers in neuroscience · 2023Review
- Biallelic variants in KARS1 are associated with neurodevelopmental disorders and hearing loss recapitulated by the knockout zebrafish.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Article
- Double mimicry evades tRNA synthetase editing by toxic vegetable-sourced non-proteinogenic amino acid.Nature communications · 2017Article
- Semi‑random mutagenesis profile of BCR‑ABL during imatinib resistance acquirement in K562 cells.Molecular medicine reports · 2017Article
- Rewiring protein synthesis: From natural to synthetic amino acids.Biochimica et biophysica acta. General subjects · 2017Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Brain and heart pathologies are caused by editing defects of transfer RNA (tRNA) synthetases, which preserve genetic code fidelity by removing incorrect amino acids misattached to tRNAs. To extend understanding of the broader impact of synthetase editing reactions on organismal homeostasis, and based on effects in bacteria ostensibly from small amounts of mistranslation of components of the replication apparatus, we investigated the sensitivity to editing of the vertebrate genome. We show here that in zebrafish embryos, transient overexpression of editing-defective valyl-tRNA synthetase (ValRS(ED)) activated DNA break-responsive H2AX and p53-responsive downstream proteins, such as cyclin-dependent kinase (CDK) inhibitor p21, which promotes cell-cycle arrest at DNA damage checkpoints, and Gadd45 and p53R2, with pivotal roles in DNA repair. In contrast, the response of these proteins to expression of ValRS(ED) was abolished in p53-deficient fish. The p53-activated downstream signaling events correlated with suppression of abnormal morphological changes caused by the editing defect and, in adults, reversed a shortened life span (followed for 2 y). Conversely, with normal editing activities, p53-deficient fish have a normal life span and few morphological changes. Whole-fish deep sequencing showed genomic mutations associated with the editing defect. We suggest that the sensitivity of p53 to expression of an editing-defective tRNA synthetase has a critical role in promoting genome integrity and organismal homeostasis.
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