非同源末端连接（NHEJ）过程中，两个 DNA 末端非共价结合的基本要素。
The essential elements for the noncovalent association of two DNA ends during NHEJ synapsis.
机构信息
Department of Pathology, Department of Biochemistry & Molecular Biology, Department of Molecular Microbiology & Immunology, and Section of Computational & Molecular Biology, USC Norris Comprehensive Cancer Center, University of Southern California Keck School of Medicine, Los Angeles, CA, 90089, USA.
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, 10016, USA.
出版信息
Nat Commun. 2019 Aug 9;10(1):3588. doi: 10.1038/s41467-019-11507-z.
One of the most central questions about the repair of a double-strand DNA break (DSB) concerns how the two free DNA ends are brought together - a step called synapsis. Using single-molecule FRET (smFRET), we show here that both Ku plus XRCC4:DNA ligase IV are necessary and sufficient to achieve a flexible synapsis of blunt DNA ends, whereas either alone is not. Addition of XLF causes a transition to a close synaptic state, and maximum efficiency of close synapsis is achieved within 20 min. The promotion of close synapsis by XLF indicates a role that is independent of a filament structure, with action focused at the very ends of each duplex. DNA-PKcs is not required for the formation of either the flexible or close synaptic states. This model explains in biochemical terms the evolutionarily central synaptic role of Ku, X4L4, and XLF in NHEJ for all eukaryotes.
双链 DNA 断裂（DSB）修复中最核心的问题之一是如何将两个游离 DNA 末端连接在一起——这一步骤称为联会。我们使用单分子荧光共振能量转移（smFRET）技术，在此表明 Ku 加 XRCC4：DNA 连接酶 IV 对于实现钝末端 DNA 的灵活联会都是必需且充分的，而单独使用任何一种都不行。添加 XLF 会导致过渡到紧密联会状态，并且在 20 分钟内实现紧密联会的最大效率。XLF 促进紧密联会表明其作用独立于细丝结构，作用集中在每个双链体的末端。DNA-PKcs 对于形成灵活或紧密联会状态都不是必需的。该模型从生化角度解释了 Ku、X4L4 和 XLF 在所有真核生物中非同源末端连接（NHEJ）中作为联会核心的进化作用。
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