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TRAX mediates the protective role of the A 2A adenosine receptor in detecting the DNA damage induced by oxidative stress
Author(s) -
Chern Yijuang,
Chien Ting,
Weng YuTing,
Chang ShuYung
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.lb184
Subject(s) - dna damage , dna repair , microbiology and biotechnology , dna , dna pkcs , biology , adenosine , homologous recombination , chemistry , biochemistry
The translin‐associated protein X (TRAX) was originally identified as an interacting protein of Translin, a DNA/RNA binding protein that controls mRNA transport, translation, DNA repair, and DNA recombination. It interacts specifically with an activator (i.e., C1D) of DNA‐dependent protein kinase (DNA‐PK) upon γ‐irradiation and thus is implicated in repair of double‐strand breaks (DSBs). We recently reported that TRAX interacts with phosphorylated ATM (Ser 1981 ) and contributes to the ATM‐mediated DNA repair in response to genotoxic stresses. The A 2A adenosine receptor (A 2A R) is a G‐protein‐coupled receptor that binds to adenosine and exists in many brain areas. Using a yeast two‐hybrid approach, we found that TRAX is an interacting protein of the cytoplasmic C terminus of A 2A R, and mediates the neuritogenesis process via KIF2A. Given that stimulation of A 2A R by two A 2A R‐selective agonists markedly ameliorates the DSBs evoked by elevated oxidative stress in human iPSCs‐derived neurons, the role of TRAX in mediating the protective role of A 2A R is of great interest. In the present study, we present evidence to suggest that TRAX is required for the A 2A R‐mediated facilitation of DNA repair in a neuronal cell line (PC12) and primary neurons. Stimulation of A 2A R appears to enhance the non‐homologous end joining (NHEJ) repair activity by increasing the activation and phosphorylation of DNA‐PK at Thr 2609 . Collectively, TRAX contributes to the activation of DNA‐PK and the detection of DSBs evoked by oxidative stress.