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A central role of TRAX in the ATM-mediated DNA repair

Oncogene volume 35, pages 1657–1670 (2016)Cite this article

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Abstract

DNA repair is critical for the maintenance of genome stability. Upon genotoxic stress, dysregulated DNA repair may induce apoptosis. Translin-associated factor X (TRAX), which was initially identified as a binding partner of Translin, has been implicated in genome stability. However, the exact role of TRAX in DNA repair remains largely unknown. Here, we showed that TRAX participates in the ATM/H2AX-mediated DNA repair machinery by interacting with ATM and stabilizing the MRN complex at double-strand breaks. The exogenous expression of wild-type (WT) TRAX, but not a TRAX variant lacking the nuclear localization signal (NLS), rescued the vulnerability of TRAX-null mouse embryo fibroblasts (MEFs). This finding confirms the importance of the nuclear localization of TRAX in the repair of DNA damage. Compared with WT MEFs, TRAX-null MEFs exhibited impaired DNA repair (for example, reduced phosphorylation of ATM and H2AX) after treatment with ultra violet-C or γ-ray irradiation and a higher incidence of p53-mediated apoptosis. Our findings demonstrate that TRAX is required for MRN complex-ATM-H2AX signaling, which optimizes DNA repair by interacting with the activated ATM and protects cells from genotoxic stress-induced apoptosis.

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Acknowledgements

We thank Hsing-Lin Lai and Shuyung Chang for technical support. This work was supported by grants from the Ministrant of Technology and Science of Taiwan (NSC96-2321-B-001-015, NSC97-2321-B-001-012 and 100-2320-B-001-0110MY3 to YC), the Institute of Biomedical Sciences of Academia Sinica (to YC) and the Kaohsiung Medical University (KMU-Q102011 to J-YW).

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  1. Department of Neurology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    J-Y Wang

  2. Neuroscience Division, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

    J-Y Wang, S-Y Chen, C-N Sun & Y Chern

  3. Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan

    T Chien & Y Chern

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Wang, JY., Chen, SY., Sun, CN. et al. A central role of TRAX in the ATM-mediated DNA repair. Oncogene 35, 1657–1670 (2016). https://doi.org/10.1038/onc.2015.228

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