2024-03-29T15:01:32Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/532692022-11-17T02:08:08Zhdl_2115_20048hdl_2115_140ER stress suppresses DNA double-strand break repair and sensitizes tumor cells to ionizing radiation by stimulating proteasomal degradation of Rad51Yamamori, TohruMeike, ShunsukeNagane, MasakiYasui, HironobuInanami, OsamuER stressRad51DNA double-strand break repairRadiosensitivityUnfolded protein response464In 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.ElsevierJournal Articleapplication/pdfhttp://hdl.handle.net/2115/53269https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/53269/1/accepted_manuscript.pdf0014-5793AA00642943FEBS Letters58720334833532013-10-11enginfo:pmid/24021650info:doi/10.1016/j.febslet.2013.08.030author