Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.29.227033v1?rss=1 Authors: Carney, S. M., Moreno, A. T., Piatt, S. C., Cisneros-Aguirre, M., Lopezcolorado, F. W., Stark, J. M., Loparo, J. J. Abstract: 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. Copy rights belong to original authors. Visit the link for more info