Structural basis for the coiled-coil architecture of human CtIP

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

doi:10.1101/2021.03.05.434060

bioRxiv · 10.1101/2021.03.05.434060

Structural basis for the coiled-coil architecture of human CtIP

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

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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 CtIPs 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.

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Morton, C. R., Rzechorzek, N. J., Maman, J. D., Kuramochi, M., Sekiguchi, H., Rambo, R. P., Sasaki, Y. C., Davies, O. R., Pellegrini, L.. 2021-03-05. Structural basis for the coiled-coil architecture of human CtIP. https://doi.org/10.1101/2021.03.05.434060

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