DNA Damage Chemistry Research Group, Institute for Quantum Life Science, National Institutes for Quantum Science and Technology, Kizugawa, 619-0215, Japan.
Program of Mathematical and Life Sciences, Graduate School of Integrated Sciences for Life, Hiroshima University, Higashi-Hiroshima 739-8526, Japan.
Proc Natl Acad Sci U S A. 2022 Mar 29;119(13):e2119132119. doi: 10.1073/pnas.2119132119. Epub 2022 Mar 24.
SignificanceDNA damage causes loss of or alterations in genetic information, resulting in cell death or mutations. Ionizing radiations produce local, multiple DNA damage sites called clustered DNA damage. In this study, a complete protocol was established to analyze the damage complexity of clustered DNA damage, wherein damage-containing genomic DNA fragments were selectively concentrated via pulldown, and clustered DNA damage was visualized by atomic force microscopy. It was found that X-rays and Fe ion beams caused clustered DNA damage. Fe ion beams also produced clustered DNA damage with high complexity. Fe ion beam-induced complex DNA double-strand breaks (DSBs) containing one or more base lesion(s) near the DSB end were refractory to repair, implying their lethal effects.
DNA 损伤会导致遗传信息的丢失或改变,从而导致细胞死亡或突变。电离辐射会产生局部的、多个 DNA 损伤位点,称为簇状 DNA 损伤。在这项研究中,建立了一个完整的方案来分析簇状 DNA 损伤的复杂性,其中通过下拉法选择性地浓缩含有损伤的基因组 DNA 片段,并通过原子力显微镜观察簇状 DNA 损伤。结果表明,X 射线和 Fe 离子束会导致簇状 DNA 损伤。Fe 离子束还会产生具有高复杂性的簇状 DNA 损伤。Fe 离子束诱导的复杂 DNA 双链断裂(DSB)在 DSB 末端附近含有一个或多个碱基损伤,难以修复,这意味着它们具有致死效应。