Ku-dependent non-homologous end-joining as the major pathway contributes to sublethal damage repair in mammalian cells

• Authors: Min Liu, Jilin University; Solah Lee, Emory University; Bailong Liu, Jilin University; Hongyan Wang, Emory University; Lihua Dong, Jilin University; Ya Wang, Emory University
• Journal Title: International Journal of Radiation Biology
• Volume: Volume 91, Number 11
• Publisher: Taylor & Francis | 2015-11-02, Pages 867-871
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.3109/09553002.2015.1075178
• Subjects: Biology, Cell; Health Sciences, Radiology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Technology; Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging; DNA DSB; DNA repair; SLDR; NHEJ; HRR; heavy ion; DOUBLE-STRAND BREAKS; ENERGY-TRANSFER RADIATION; DNA-LIGASE-IV; X-RAY DAMAGE; HOMOLOGOUS RECOMBINATION; IONIZING-RADIATION; CYCLE; RECOVERY; BRACHYTHERAPY; RADIOTHERAPY

Abstract

Purpose: Sublethal damage repair (SLDR) is a type of repair that occurs in split dose irradiated cells, which was discovered more than 50 years ago. However, due to conflicting reported data, it remains unclear which DNA double strand break (DSB) repair pathway, non-homologous end-joining (NHEJ) repair, homologous recombination repair (HRR) or both, contributes to SLDR, particularly in human cells. We were interested in clarifying this question. Methods and materials: Mammalian cell lines, including human, mouse and Chinese hamster ovary (CHO) cell lines, wild type, deficient in NHEJ or HRR were irradiated with either single dose or two split doses at 2 or 4 hour intervals. The clonogenic assay was used to evaluate these cell radiosensitivities. Results: All wild type or HRR deficient cells (including human, mouse and CHO cells) showed a higher survival rate after exposure to split dose versus single dose radiation, however, all classical NHEJ deficient cells (including human, mouse and hamster cells) did not show any apparent sensitivity changes between single dose and split dose irradiation. Conclusion: Classical NHEJ mainly contributes to SLDR in mammalian cells (including human cells) cells. These results have the potential to improve radiotherapy.