ER stress suppresses DNA double-strand break repair and sensitizes tumor cells to ionizing radiation by stimulating proteasomal degradation of Rad51

FEBS Lett. 2013 Oct 11;587(20):3348-53. doi: 10.1016/j.febslet.2013.08.030. Epub 2013 Sep 7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Line, Tumor
  • DNA Breaks, Double-Stranded / drug effects*
  • DNA Repair / genetics
  • DNA Repair / radiation effects*
  • Electrophoresis, Polyacrylamide Gel
  • Endoplasmic Reticulum Stress / genetics
  • Endoplasmic Reticulum Stress / radiation effects
  • Humans
  • Proteasome Endopeptidase Complex / metabolism*
  • Rad51 Recombinase / genetics
  • Rad51 Recombinase / metabolism*
  • Radiation, Ionizing*
  • Reverse Transcriptase Polymerase Chain Reaction


  • Rad51 Recombinase
  • Proteasome Endopeptidase Complex