title: 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.
authors.affiliation: Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Yamamori
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Meike
authors.forename: Masaki
authors.initials: M
authors.lastname: Nagane
authors.forename: Hironobu
authors.initials: H
authors.lastname: Yasui
authors.forename: Osamu
authors.initials: O
authors.lastname: Inanami
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects*; D004260:DNA Repair / Q000235:genetics / Q000528:radiation effects*; D004591:Electrophoresis, Polyacrylamide Gel; D059865:Endoplasmic Reticulum Stress / Q000235:genetics / Q000528:radiation effects; D006801:Humans; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism*; D011839:Radiation, Ionizing; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051135:Rad51 Recombinase; D046988:Proteasome Endopeptidase Complex
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