CtIP forms a tetrameric dumbbell-shaped particle which bridges complex DNA end structures for double-strand break repair
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Published version
OA Location
Author(s)
Type
Journal Article
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.
Date Issued
2019-01-02
Date Acceptance
2019-01-01
Citation
eLife, 2019, 8
ISSN
2050-084X
Publisher
eLife Sciences Publications Ltd
Journal / Book Title
eLife
Volume
8
Copyright Statement
© 2019 Wilkinson et al. This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited.
Sponsor
Cancer Research UK
Wellcome Trust
Cancer Research UK
Wellcome Trust
Wellcome Trust
Grant Number
12799
202926/Z/16/Z
C6913/A21608
206175/Z/17/Z
212938/Z/18/Z
Publication Status
Published
Article Number
e42129
Date Publish Online
2019-01-02