ER stress suppresses DNA double-strand break repair and sensitizes tumor cells to ionizing radiation by stimulating proteasomal degradation of Rad51
- PMID: 24021650
- DOI: 10.1016/j.febslet.2013.08.030
ER stress suppresses DNA double-strand break repair and sensitizes tumor cells to ionizing radiation by stimulating proteasomal degradation of Rad51
Abstract
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.
Keywords: DNA double-strand break repair; DSB; ER; ER stress; ER-associated degradation; ERAD; HR; IR; NHEJ; RT-PCR; Rad51; Radiosensitivity; UPR; Unfolded protein response; double-strand break; endoplasmic reticulum; homologous recombination; ionizing radiation; non-homologous end joining; reverse transcription-PCR; unfolded protein response.
Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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