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Updated: Apr 9, 2026
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Published on: June 26, 2020
A central role of TRAX in the ATM-mediated DNA repair
J-Y Wang1,2, S-Y Chen2, C-N Sun2
1Department of Neurology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
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.
Insights
Translin-associated factor X (TRAX) is crucial for DNA repair, stabilizing key protein complexes at double-strand breaks. Nuclear TRAX optimizes DNA repair signaling and protects cells from genotoxic stress-induced apoptosis.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- DNA repair is essential for maintaining genome stability.
- Dysregulated DNA repair can lead to apoptosis under genotoxic stress.
- The precise function of Translin-associated factor X (TRAX) in DNA repair is not well understood.
Purpose of the Study:
- To elucidate the role of TRAX in DNA double-strand break repair.
- To investigate TRAX's interaction with the ATM/H2AX DNA repair pathway.
- To determine the significance of TRAX's nuclear localization in DNA damage response.
Main Methods:
- Investigated TRAX interaction with ATM and the MRN complex.
- Utilized TRAX-null mouse embryo fibroblasts (MEFs) and wild-type (WT) TRAX rescue experiments.
- Assessed DNA repair efficacy via ATM and H2AX phosphorylation after UV-C and gamma-ray irradiation.
- Quantified p53-mediated apoptosis incidence.
Main Results:
- TRAX interacts with ATM and stabilizes the MRN complex at double-strand breaks.
- Nuclear localization of TRAX is essential for its DNA repair function.
- TRAX-null MEFs show impaired DNA repair, reduced ATM/H2AX phosphorylation, and increased apoptosis compared to WT MEFs.
- TRAX is required for the MRN complex-ATM-H2AX signaling pathway.
Conclusions:
- TRAX plays a vital role in the ATM/H2AX-mediated DNA repair pathway.
- TRAX optimizes DNA repair by interacting with activated ATM and protecting cells from genotoxic stress.
- Nuclear TRAX is critical for efficient DNA damage response and prevention of apoptosis.
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