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Oxidative stress diverts tRNA synthetase to nucleus for protection against DNA damage.

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.

SUBMITTER: Wei N

PROVIDER: S-EPMC4224670 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Oxidative stress diverts tRNA synthetase to nucleus for protection against DNA damage.

Wei Na N Shi Yi Y Truong Lan N LN Fisch Kathleen M KM Xu Tao T Gardiner Elisabeth E Fu Guangsen G Hsu Yun-Shiuan Olivia YO Kishi Shuji S Su Andrew I AI Wu Xiaohua X Yang Xiang-Lei XL

Molecular cell 20141002 2

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 ...[more]

PMID: 25284223

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Project description:Caesalpinia crista is a medicinal herb used to cure various ailments in subtropical and tropical regions of Southeast Asia.The objective of this evaluation of C. crista against free radical induced DNA and erythrocyte damage.The profiles of polyphenol and flavonoid were quantified through reversed-phase high-performance liquid chromatography. Free radical induced DNA and membrane damage were performed using H2O2 as oxidative agent.The total polyphenol content of C. crista leaf ethyl acetate extract (CcEA) was 94.5 ± 3.8 mg/gGAE, CcME (C. crista leaf methanol extract) was 52.7 ± 2.8 mg/gGAE, and CcWE (C. crista leaf Water extract) was 31.84 ± 1.8 mg/gGAE. Total flavonoid content of CcEA was 60.46 ± 2.3 mg/gQE, CcME was 46.26 ± 1.8 mg/gQE, and CcWE was 20.47 ± 1.1 mg/gQE. The extracts also exhibited good antioxidant activity as confirmed by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid), hydroxyl scavenging, reducing power, and total antioxidant assays. Among the three extracts, CcEA and CcME showed better protection against red blood cell (RBC) hemolysis and DNA damage as confirmed by electrophoretic study. Further, Scanning electron micrograph data showed that CcEA revealed the free radical induced structural alterations in RBC.These findings suggest that C. crista contains bioactive molecules and can inhibit oxidative stress and can be source of further study to use this in herbal medicine.ROS are generated under normal biological systems. These ROS generated can be scavenged by endogenous and exogenous cellular mechanisms. Environmental stress, radiation, smoke etc. elevates ROS dramatically. This leads to significant damage to cellular biomolecules like DNA and cell structures. Plants as a large reservoir of drugs for protecting DNA and cell structures from oxidative stress. Polyphenols present in the C. crista extracts acts through several mechanisms to quench free radicals. Extracts exhibited potent antioxidant properties and also protected DNA and cell membrane from oxidative damage. Hence this can be used in herbal medicine for treating oxidative stress mediated diseases. Abbreviations used: ABTS: 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid); CcEA: C. crista leaf ethyl acetate extract; CcME: C. crista leaf methanol extract; CcWE: C. crista leaf Water extract; DPPH: 2,2-diphenyl-1-picrylhydrazyl; GAE: Gallic acid Equivalent; H2O2: Hydrogen Peroxide; QE: Quercetin Equivalent; RNS: Reactive Nitrogen Spevcies; ROS: Reactive Oxygen Species; SEM: Scanning Electron Microscope.

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Oxidative stress diverts tRNA synthetase to nucleus for protection against DNA damage.

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Oxidative stress diverts tRNA synthetase to nucleus for protection against DNA damage.

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