Ku-dependent non-homologous end-joining as the major pathway contributes to sublethal damage repair in mammalian cells
Ku-dependent non-homologous end-joining as the major pathway contributes to sublethal damage repair in mammalian cells
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DOI：
10.3109/09553002.2015.1075178
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发表时间：
2015-11-02
影响因子：
2.6
通讯作者：
Wang, Ya
中科院分区：
文献类型：
--
作者：
Liu, Min;Lee, Solah;Wang, Ya
目的：亚致死损伤修复 (SLDR) 是一种发生在分次剂量辐照细胞中的修复类型，于 50 多年前被发现。然而，由于报道的数据相互矛盾，目前尚不清楚哪种 DNA 双链断裂 (DSB) 修复途径、非同源末端连接 (NHEJ) 修复、同源重组修复 (HRR) 或两者共同导致 SLDR，特别是在人类细胞中。我们有兴趣澄清这个问题。方法和材料：野生型、NHEJ 或 HRR 缺陷的哺乳动物细胞系，包括人、小鼠和中国仓鼠卵巢 (CHO) 细胞系，以单剂量或间隔 2 或 4 小时分两次剂量进行照射。克隆形成试验用于评估这些细胞的放射敏感性。结果：所有野生型或 HRR 缺陷细胞（包括人、小鼠和 CHO 细胞）在暴露于分次剂量辐射后与单剂量辐射相比表现出更高的存活率；然而，所有经典NHEJ缺陷细胞（包括人类、小鼠和仓鼠细胞）在单剂量和分次剂量照射之间没有表现出任何明显的敏感性变化。结论：经典NHEJ主要导致哺乳动物细胞（包括人类细胞）的SLDR。这些结果有可能改善放射治疗。
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-h 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). These results have the potential to improve radiotherapy.