Hou Zhiyang, Xu Zelin, Wu Mengying, Ma Liqiu, Sui Li, Bian Po, Wang Ting
Teaching and Research Section of Nuclear Medicine, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China.
Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China.
Biology (Basel). 2023 Nov 7;12(11):1406. doi: 10.3390/biology12111406.
Repeat-mediated deletion (RMD) rearrangement is a major source of genome instability and can be deleterious to the organism, whereby the intervening sequence between two repeats is deleted along with one of the repeats. RMD rearrangement is likely induced by DNA double-strand breaks (DSBs); however, it is unclear how the complexity of DSBs influences RMD rearrangement. Here, a transgenic strain K12 MG1655 with a repeat-controlled amp activation was used while taking advantage of particle irradiation, such as proton and carbon irradiation, to generate different complexities of DSBs. Our research confirmed the enhancement of RMD under proton and carbon irradiation and revealed a positive correlation between RMD enhancement and LET. In addition, RMD enhancement could be suppressed by an intermolecular homologous sequence, which was regulated by its composition and length. Meanwhile, RMD enhancement was significantly stimulated by exogenous λ-Red recombinase. Further results investigating its mechanisms showed that the enhancement of RMD, induced by particle irradiation, occurred in a -dependent manner. Our finding has a significant impact on the understanding of RMD rearrangement and provides some clues for elucidating the repair process and possible outcomes of complex DNA damage.
重复介导的缺失（RMD）重排是基因组不稳定的主要来源，可能对生物体有害，即两个重复序列之间的间隔序列会与其中一个重复序列一起被删除。RMD重排可能由DNA双链断裂（DSB）诱导；然而，尚不清楚DSB的复杂性如何影响RMD重排。在此，利用粒子辐射，如质子和碳离子辐射，产生不同复杂性的DSB，使用了具有重复控制的氨苄激活的转基因菌株K12 MG1655。我们的研究证实了质子和碳离子辐射下RMD的增强，并揭示了RMD增强与传能线密度（LET）之间的正相关关系。此外，分子间同源序列可抑制RMD增强，其受组成和长度的调节。同时，外源性λ-Red重组酶显著刺激RMD增强。进一步研究其机制的结果表明，粒子辐射诱导的RMD增强以一种-依赖性方式发生。我们的发现对理解RMD重排具有重要意义，并为阐明复杂DNA损伤的修复过程和可能结果提供了一些线索。
