Structural basis for the coiled-coil architecture of human CtIP

C. R. Morton, N. J. Rzechorzek, J. D. Maman, M. Kuramochi, H. Sekiguchi, R. Rambo, Y. C. Sasaki, O. R. Davies, L. Pellegrini

Research output: Working paper

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 recombinational repair. The zinc-binding motif in CtIP’s 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.
Original languageEnglish
PublisherbioRxiv, at Cold Spring Harbor Laboratory
DOIs
Publication statusPublished - 5 Mar 2021

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