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.
Similar articles
-
Tumor cell kill by c-MYC depletion: role of MYC-regulated genes that control DNA double-strand break repair.Cancer Res. 2010 Nov 1;70(21):8748-59. doi: 10.1158/0008-5472.CAN-10-0944. Epub 2010 Oct 12. Cancer Res. 2010. PMID: 20940401
-
Regulation of ATM in DNA double strand break repair accounts for the radiosensitivity in human cells exposed to high linear energy transfer ionizing radiation.Mutat Res. 2009 Nov 2;670(1-2):15-23. doi: 10.1016/j.mrfmmm.2009.06.016. Epub 2009 Jul 5. Mutat Res. 2009. PMID: 19583974
-
β1-Integrin Impacts Rad51 Stability and DNA Double-Strand Break Repair by Homologous Recombination.Mol Cell Biol. 2018 Apr 16;38(9):e00672-17. doi: 10.1128/MCB.00672-17. Print 2018 May 1. Mol Cell Biol. 2018. PMID: 29463647 Free PMC article.
-
Genetic variations in DNA repair genes, radiosensitivity to cancer and susceptibility to acute tissue reactions in radiotherapy-treated cancer patients.Acta Oncol. 2008;47(5):809-24. doi: 10.1080/02841860801885969. Acta Oncol. 2008. PMID: 18568480 Review.
-
Targeting DNA Double-Strand Break (DSB) Repair to Counteract Tumor Radio-resistance.Curr Drug Targets. 2019;20(9):891-902. doi: 10.2174/1389450120666190222181857. Curr Drug Targets. 2019. PMID: 30806313 Review.
Cited by
-
SPRTN is involved in hepatocellular carcinoma development through the ER stress response.Cancer Gene Ther. 2024 Mar;31(3):376-386. doi: 10.1038/s41417-023-00708-w. Epub 2023 Dec 12. Cancer Gene Ther. 2024. PMID: 38086993
-
DNA damage repair is suppressed in porcine aged oocytes.J Anim Sci Technol. 2021 Sep;63(5):984-997. doi: 10.5187/jast.2021.e90. Epub 2021 Sep 30. J Anim Sci Technol. 2021. PMID: 34796342 Free PMC article.
-
Keap1 mutation renders lung adenocarcinomas dependent on Slc33a1.Nat Cancer. 2020 Jun;1(6):589-602. doi: 10.1038/s43018-020-0071-1. Epub 2020 Jun 8. Nat Cancer. 2020. PMID: 34414377 Free PMC article.
-
Adaptation to Endoplasmic Reticulum Stress Enhances Resistance of Oral Cancer Cells to Cisplatin by Up-Regulating Polymerase η and Increasing DNA Repair Efficiency.Int J Mol Sci. 2020 Dec 31;22(1):355. doi: 10.3390/ijms22010355. Int J Mol Sci. 2020. PMID: 33396303 Free PMC article.
-
Targeting c-Myc Unbalances UPR towards Cell Death and Impairs DDR in Lymphoma and Multiple Myeloma Cells.Biomedicines. 2022 Mar 22;10(4):731. doi: 10.3390/biomedicines10040731. Biomedicines. 2022. PMID: 35453482 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials