TY - JOUR TI - CtIP forms a tetrameric dumbbell-shaped particle which bridges complex DNA end structures for double-strand break repair AU - Wilkinson, Oliver J AU - Martín-González, Alejandro AU - Kang, Haejoo AU - Northall, Sarah J AU - Wigley, Dale B AU - Moreno-Herrero, Fernando AU - Dillingham, Mark Simon A2 - Spies, Maria A2 - Kuriyan, John VL - 8 PY - 2019 DA - 2019/01/02 SP - e42129 C1 - eLife 2019;8:e42129 DO - 10.7554/eLife.42129 UR - https://doi.org/10.7554/eLife.42129 AB - CtIP is involved in the resection of broken DNA during the S and G2 phases of the cell cycle for repair by recombination. Acting with the MRN complex, it plays a particularly important role in handling complex DNA end structures by localised nucleolytic processing of DNA termini in preparation for longer range resection. Here we show that human CtIP is a tetrameric protein adopting a dumbbell architecture in which DNA binding domains are connected by long coiled-coils. The protein complex binds two short DNA duplexes with high affinity and bridges DNA molecules in trans. DNA binding is potentiated by dephosphorylation and is not specific for DNA end structures per se. However, the affinity for linear DNA molecules is increased if the DNA terminates with complex structures including forked ssDNA overhangs and nucleoprotein conjugates. This work provides a biochemical and structural basis for the function of CtIP at complex DNA breaks. KW - homologous recombination KW - Sae2 KW - DNA end resection KW - atomic force microscopy KW - DNA repair KW - double-stranded DNA break repair JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -