RT Journal Article
SR Electronic
T1 Human CtIP forms a tetrameric dumbbell-shaped particle which binds and bridges complex DNA end structures for double-strand break repair
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 409102
DO 10.1101/409102
A1 O.J. Wilkinson
A1 A. Martín-González
A1 H.J. Kang
A1 S.J. Northall
A1 D.B. Wigley
A1 F. Moreno-Hererro
A1 M.S. Dillingham
YR 2018
UL http://biorxiv.org/content/early/2018/09/05/409102.abstract
AB CtIP is involved in the resection of double-stranded DNA breaks during the S and G2 phases of the cell cycle for repair by homologous recombination. Acting in concert 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 more complex structures including forked ssDNA overhangs and model nucleoprotein conjugates. This work provides a biochemical and structural basis for the function of CtIP at complex DNA breaks.