4X01: S. Pombe Ctp1 Tetramerization Domain

Citation:
Abstract
Ctp1 (also known as CtIP or Sae2) collaborates with Mre11-Rad50-Nbs1 to initiate repair of DNA double-strand breaks (DSBs), but its functions remain enigmatic. We report that tetrameric Schizosaccharomyces pombe Ctp1 contains multivalent DNA-binding and DNA-bridging activities. Through structural and biophysical analyses of the Ctp1 tetramer, we define the salient features of Ctp1 architecture: an N-terminal interlocking tetrameric helical dimer-of-dimers (THDD) domain and a central intrinsically disordered region (IDR) linked to C-terminal 'RHR' DNA-interaction motifs. The THDD, IDR and RHR are required for Ctp1 DNA-bridging activity in vitro, and both the THDD and RHR are required for efficient DSB repair in S. pombe. Our results establish non-nucleolytic roles of Ctp1 in binding and coordination of DSB-repair intermediates and suggest that ablation of human CtIP DNA binding by truncating mutations underlie the CtIP-linked Seckel and Jawad syndromes.
PDB ID: 4X01Download
MMDB ID: 126153
PDB Deposition Date: 2014/11/20
Updated in MMDB: 2017/09
Experimental Method:
x-ray diffraction
Resolution: 2.2  Å
Source Organism:
Similar Structures:
Biological Unit for 4X01: tetrameric; determined by author
Molecular Components in 4X01
Label Count Molecule
Proteins (4 molecules)
4
DNA Binding Ctp1(Gene symbol: ctp1)
Molecule annotation
Chemicals (9 molecules)
1
9
* Click molecule labels to explore molecular sequence information.

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