4X01

S. pombe Ctp1 tetramerization domain

Summary for 4X01

• Entry DOI: 10.2210/pdb4x01/pdb
• Descriptor: DNA binding ctp1, 1,2-ETHANEDIOL (3 entities in total)
• Functional Keywords: homologous recombination, dna double-strand break repair, dna binding, four-helix bundle, dna binding protein
• Biological source: Schizosaccharomyces pombe (Fission yeast)
• Total number of polymer chains: 8
• Total formula weight: 55614.87

Authors

Andres, S.N.,Williams, R.S. (deposition date: 2014-11-20, release date: 2015-01-14, Last modification date: 2023-09-27)

Primary citation

Andres, S.N.,Appel, C.D.,Westmoreland, J.W.,Williams, J.S.,Nguyen, Y.,Robertson, P.D.,Resnick, M.A.,Williams, R.S.
Tetrameric Ctp1 coordinates DNA binding and DNA bridging in DNA double-strand-break repair.
Nat.Struct.Mol.Biol., 22:158-166, 2015

PubMed 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.

PubMed: 25580577
DOI: 10.1038/nsmb.2945

Experimental method

X-RAY DIFFRACTION (2.201 Å)