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

• Type of Material: Article
• 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
• Language: English
• Date: 2015-11-02
• Publisher: Taylor & Francis
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 Informa UK, Ltd.
• Final Published Version (URL): http://dx.doi.org/10.3109/09553002.2015.1075178
• Title of Journal or Parent Work: International Journal of Radiation Biology
• ISSN: 0955-3002
• Volume: 91
• Issue: 11
• Start Page: 867
• End Page: 871
• Grant/Funding Information: This work is supported by grants from the National Aeronautics and Space Administration (NNX11AC30G to Y.W.) and the National Cancer Institute (P30CA138292 to the Institute).
• Keywords: DNA DSB; RECOVERY; Technology; ENERGY-TRANSFER RADIATION; IONIZING-RADIATION; Radiology, Nuclear Medicine & Medical Imaging; Life Sciences & Biomedicine; Nuclear Science & Technology; NHEJ; DNA repair; RADIOTHERAPY; BRACHYTHERAPY; CYCLE; X-RAY DAMAGE; Science & Technology; Biology; DOUBLE-STRAND BREAKS; HRR; heavy ion; DNA-LIGASE-IV; SLDR; HOMOLOGOUS RECOMBINATION

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.