The essential elements for the noncovalent association of two DNA ends during NHEJ synapsis
The essential elements for the noncovalent association of two DNA ends during NHEJ synapsis
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DOI：
10.1038/s41467-019-11507-z
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发表时间：
2019-08-09
影响因子：
16.6
通讯作者：
Lieber, Michael R.
中科院分区：
文献类型：
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作者：
Zhao, Bailin;Watanabe, Go;Lieber, Michael R.
关于修复双链DNA断裂（DSB）的最核心问题之一是两个游离DNA末端如何结合在一起-这一步骤称为突触。使用单分子FRET（smFRET），我们在这里表明，这两个Ku加上XRCC 4：DNA连接酶IV是必要的，足以实现一个灵活的突触钝的DNA末端，而单独不是。此外XLF的原因过渡到一个紧密的突触状态，并在20分钟内实现最大效率的紧密突触。XLF的促进紧密突触表示的作用，是独立的细丝结构，与行动集中在每个双链体的末端。DNA-PKcs不是形成灵活或紧密突触状态所必需的。该模型解释了在生物化学方面的Ku，X4 L4，和XLF在NHEJ的所有真核生物的进化中央突触的作用。
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.