Non-homologous end joining (NHEJ) is the predominant pathway that repairs DNA double strand breaks in vertebrates. During NHEJ DNA ends are held together by a multi-protein synaptic complex until they are ligated. Here we investigate the role of the intrinsically disordered C-terminal tail of XLF, a critical factor in end synapsis. We demonstrate that the XLF tail along with the Ku binding motif (KBM) at the extreme C-terminus are required for end joining. While the underlying sequence of the tail can be varied, a minimal tail length is required for NHEJ. Single-molecule FRET experiments that observe end synapsis in real-time show that this defect is due to a failure to closely align DNA ends. Our data supports a model in which a single C-terminal tail tethers XLF to Ku while allowing XLF to form interactions with XRCC4 that enable synaptic complex formation.

中文翻译：

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XLF在非同源端接期间用作柔性连接器

非同源末端连接（NHEJ）是修复脊椎动物DNA双链断裂的主要途径。在NHEJ期间，DNA末端由多蛋白突触复合物连接在一起，直到连接为止。在这里，我们调查XLF固有的无序C末端尾巴的作用，这是最终突触的关键因素。我们证明XLF尾部以及在极端C端的Ku结合基序（KBM）都是末端连接所必需的。尽管尾部的基本序列可以变化，但NHEJ要求最小的尾部长度。实时观察末端突触的单分子FRET实验表明，该缺陷是由于未能紧密对齐DNA末端所致。