TY - JOUR TI - XLF acts as a flexible connector during non-homologous end joining AU - Carney, Sean M AU - Moreno, Andrew T AU - Piatt, Sadie C AU - Cisneros-Aguirre, Metztli AU - Lopezcolorado, Felicia Wednesday AU - Stark, Jeremy M AU - Loparo, Joseph J A2 - Spies, Maria A2 - Wolberger, Cynthia A2 - Strick, Terence VL - 9 PY - 2020 DA - 2020/12/08 SP - e61920 C1 - eLife 2020;9:e61920 DO - 10.7554/eLife.61920 UR - https://doi.org/10.7554/eLife.61920 AB - 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 use Xenopus laevis egg extract to investigate the role of the intrinsically disordered C-terminal tail of the XRCC4-like factor (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. Although 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. KW - DNA repair KW - non-homologous end joining KW - DNA double strand break KW - single-molecule FRET JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -