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
-
Nodakenin Induces ROS-Dependent Apoptotic Cell Death and ER Stress in Radioresistant Breast Cancer.Antioxidants (Basel). 2023 Feb 15;12(2):492. doi: 10.3390/antiox12020492. Antioxidants (Basel). 2023. PMID: 36830050 Free PMC article.
-
Tumor-derived exosomes (TDEs): How to avoid the sting in the tail.Med Res Rev. 2020 Jan;40(1):385-412. doi: 10.1002/med.21623. Epub 2019 Jul 18. Med Res Rev. 2020. PMID: 31318078 Free PMC article. Review.
-
Strong adverse prognostic impact of hyperglycemic episodes during adjuvant chemoradiotherapy of glioblastoma multiforme.Strahlenther Onkol. 2014 Oct;190(10):933-8. doi: 10.1007/s00066-014-0696-z. Epub 2014 Jun 18. Strahlenther Onkol. 2014. PMID: 24938515
-
RNA sequencing identifies novel regulated IRE1-dependent decay targets that affect multiple myeloma survival and proliferation.Exp Hematol Oncol. 2022 Mar 31;11(1):18. doi: 10.1186/s40164-022-00271-4. Exp Hematol Oncol. 2022. PMID: 35361260 Free PMC article.
-
Inhibition of Protein Disulfide Isomerase (PDIA1) Leads to Proteasome-Mediated Degradation of Ubiquitin-like PHD and RING Finger Domain-Containing Protein 1 (UHRF1) and Increased Sensitivity of Glioblastoma Cells to Topoisomerase II Inhibitors.ACS Pharmacol Transl Sci. 2022 Dec 7;6(1):100-114. doi: 10.1021/acsptsci.2c00186. eCollection 2023 Jan 13. ACS Pharmacol Transl Sci. 2022. PMID: 36654750 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials