期刊
OPEN BIOLOGY
卷 11, 期 6, 页码 -出版社
ROYAL SOC
DOI: 10.1098/rsob.210060
关键词
human CtIP; DNA repair; coiled-coil structure
资金
- Wellcome Trust investigator award [104641/Z/14/Z]
- [219413/Z/19/Z]
- Wellcome Trust [104641/Z/14/Z] Funding Source: Wellcome Trust
This study presents an atomic model for the three-dimensional architecture of human CtIP, revealing its critical role in DNA repair through a multi-disciplinary approach. The data show that CtIP adopts a dimer-of-dimers structure and the zinc-binding motif in the N-terminus alters the coiled-coil structure, affecting CtIP's interactions with DNA. These results provide a structural basis for understanding CtIP's function in DNA DSB repair.
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.
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