DNA Ligase IV Guides End-Processing Choice during Nonhomologous End Joining

• DOI: 10.1016/j.celrep.2017.08.091
• Publication Date: 2017-09-19T19:25:00Z
• Authors: Michael P. Conlin; Dylan A. Reid; George W. Small; Howard H. Chang; Go Watanabe; Michael R. Lieber; Dale A. Ramsden; Eli Rothenberg
• Keywords: Non-homologous end joining; End-to-end principle; DNA Ligases

Highlights•Mobility of DNA ends aligned by NHEJ factors increases when are mispaired•Increased end mobility requires insert1, a motif unique to the ligase (LIG4)•End mobilization is also essential for cellular repair damaged and mispaired ends•This mechanism explains remarkable flexibility in diverse endsSummaryNonhomologous joining (NHEJ) must adapt structures during chromosome breaks. Here, we investigate mechanistic basis this flexibility. paired-end complex (PEC) Ku, XLF, XRCC4, IV (LIG4); show single-molecule analysis how terminal mispairs lead within PECs consequent sampling more end-alignment configurations. This remodeling direct ligation NHEJ, since such both require LIG4-specific structural motif, insert1. Insert1 required PEC that enables nucleolytic processing block ligation. Accordingly, cells expressing LIG4 lacking insert1 sensitive ionizing radiation. Cellular thus identifies steps necessary through LIG4-mediated sensing differences structure dynamic ends.Graphical abstract