CtIP forms a tetrameric dumbbell-shaped particle which bridges complex DNA end structures for double-strand break repair
- University of Bristol, United Kingdom
- Centro Nacional de Biotecnologia, Consejo Superior de Investigaciones Cientificas, Spain
- Imperial College London, United Kingdom
Abstract
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Fernando Moreno-Herrero
Mark Simon Dillingham
Funding
Wellcome (100401/Z/12/Z)
- Oliver J Wilkinson
- Sarah J Northall
- Mark Simon Dillingham
Cancer Research UK (C6913/A21608)
- Haejoo Kang
- Dale B Wigley
Spanish Ministry of Science (BFU2017-83794-P)
- Fernando Moreno-Herrero
European Research Council (681299)
- Fernando Moreno-Herrero
Spanish MINECO (BES-2015-071244)
- Alejandro Martín-González
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Wilkinson et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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CtIP forms a tetrameric dumbbell-shaped particle which bridges complex DNA end structures for double-strand break repair
eLife 8:e42129.
https://doi.org/10.7554/eLife.42129
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