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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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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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