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ER stress suppresses DNA double‐strand break repair and sensitizes tumor cells to ionizing radiation by stimulating proteasomal degradation of Rad51
Author(s) -
Yamamori Tohru,
Meike Shunsuke,
Nagane Masaki,
Yasui Hironobu,
Inanami Osamu
Publication year - 2013
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.08.030
Subject(s) - rad51 , ionizing radiation , degradation (telecommunications) , dna damage , chemistry , dna , cancer research , dna repair , biophysics , irradiation , double strand , microbiology and biotechnology , biology , biochemistry , physics , nuclear physics , telecommunications , computer science
In this study, we provide evidence that endoplasmic reticulum (ER) stress suppresses DNA double‐strand break (DSB) repair and increases radiosensitivity of tumor cells by altering Rad51 levels. We show that the ER stress inducer tunicamycin stimulates selective degradation of Rad51 via the 26S proteasome, impairing DSB repair and enhancing radiosensitivity in human lung cancer A549 cells. We also found that glucose deprivation, which is a physiological inducer of ER stress, triggered similar events. These findings suggest that ER stress caused by the intratumoral environment influences tumor radiosensitivity, and that it has potential as a novel target to improve cancer radiotherapy.