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

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

Author information

1
Laboratory of Radiation Biology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan.

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

PMID:
24021650
DOI:
10.1016/j.febslet.2013.08.030
[Indexed for MEDLINE]
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