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Structural basis for the coiled-coil architecture of human CtIP

DOI: 10.1098/rsob.210060 DOI Help

Authors: C. R. Morton (University of Cambridge) , N. J. Rzechorzek (University of Cambridge) , J. D. Maman (University of Cambridge) , M. Kuramochi (The University of Tokyo; National Institute of Advanced Industrial Science and Technology) , H. Sekiguchi (Japan Synchrotron Radiation Research Institute) , R. Rambo (Diamond Light Source) , Y. C. Sasaki (The University of Tokyo; National Institute of Advanced Industrial Science and Technology; Japan Synchrotron Radiation Research Institute) , O. R. Davies (University of Edinburgh) , Luca Pellegrini (University of Cambridge)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Open Biology , VOL 11

State: Published (Approved)
Published: June 2021

Open Access Open Access

Abstract: The DNA repair factor CtIP has a critical function in double-strand break (DSB) repair by homologous recombination, promoting the assembly of the repair apparatus at DNA ends and participating in DNA-end resection. However, the molecular mechanisms of CtIP function in DSB repair remain unclear. Here, we present an atomic model for the three-dimensional architecture of human CtIP, derived from a multi-disciplinary approach that includes X-ray crystallography, small-angle X-ray scattering (SAXS) and diffracted X-ray tracking (DXT). Our data show that CtIP adopts an extended dimer-of-dimers structure, in agreement with a role in bridging distant sites on chromosomal DNA during the recombinational repair. The zinc-binding motif in the CtIP N-terminus alters dynamically the coiled-coil structure, with functional implications for the long-range interactions of CtIP with DNA. Our results provide a structural basis for the three-dimensional arrangement of chains in the CtIP tetramer, a key aspect of CtIP function in DNA DSB repair.

Journal Keywords: human CtIP; coiled-coil structure; DNA repair

Subject Areas: Biology and Bio-materials, Chemistry

Instruments: B16-Test Beamline , B21-High Throughput SAXS

Added On: 21/06/2021 14:55


Discipline Tags:

Life Sciences & Biotech Biophysics Structural biology Chemistry Biochemistry

Technical Tags:

Scattering Small Angle X-ray Scattering (SAXS)