The Ku-dependent non-homologous end-joining pathway contributes to low-dose radiation-stimulated cell survival.
Low-dose (≤0.1 Gy) radiation-induced adaptive responses could protect cells from high-challenge dose radiation-induced killing. The protective role is believed to promote the repair of DNA double-strand breaks (DSBs) that are a severe threat to cell survival. However, it remains unclear which repair pathway, homologous recombination repair (HRR) or non-homologous end-joining (NHEJ), is promoted by low-dose radiation. To address this question, we examined the effects of low-dose (0.1 Gy) on high-challenge dose (2-4 Gy) induced killing in NHEJ- or HRR-deficient cell lines. We showed that 0.1 Gy reduced the high-dose radiation-induced killing for wild-type or HRR-deficient cells, but enhanced the killing for NHEJ-deficient cells. Interestingly, low-dose radiation also enhanced the killing for wild-type cells exposed to high-challenge dose radiation with high-linear energy transfer (LET). Because it is known that high-LET radiation induces an inefficient NHEJ, these results support that the low-dose radiation-stimulated protective role in reducing high-challenge dose (low-LET)-induced cell killing might depend on NHEJ. In addition, we showed that low-dose radiation activated the DNA-PK catalytic subunit (DNA-PKcs) and the inhibitor of DNA-PKcs destroyed the low-dose radiation-induced protective role. These results suggest that low-dose radiation might promote NHEJ through the stimulation of DNA-PKcs activity and; therefore, increase the resistance of cells to high-challenge dose radiation-induced killing.
Yu
Xiaoyan
X
Department of Radiation Oncology, Emory University School of Medicine, Winship Cancer Institute of Emory University, Atlanta, Georgia 30322, USA.
Wang
Hongyan
H
Wang
Ping
P
Chen
Benjamin P C
BP
Wang
Ya
Y
D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics / Q000378:metabolism*; D016466:CHO Cells / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects*; D006224:Cricetinae; D003412:Cricetulus; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology / Q000528:radiation effects; D006367:HeLa Cells / Q000528:radiation effects; D006801:Humans; D000072200:Ku Autoantigen; D051379:Mice; D011995:Recombination, Genetic
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; C000606509:Xrcc6 protein, human; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen