PT  - JOURNAL ARTICLE
AU  - C. R. Morton
AU  - N. J. Rzechorzek
AU  - J. D. Maman
AU  - M. Kuramochi
AU  - H. Sekiguchi
AU  - R. Rambo
AU  - Y. C. Sasaki
AU  - O. R. Davies
AU  - L. Pellegrini
TI  - Structural basis for the coiled-coil architecture of human CtIP
AID  - 10.1101/2021.03.05.434060
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.03.05.434060
4099  - http://biorxiv.org/content/early/2021/03/05/2021.03.05.434060.short
4100  - http://biorxiv.org/content/early/2021/03/05/2021.03.05.434060.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.