4x01
From Proteopedia
S. pombe Ctp1 tetramerization domain
Structural highlights
Function[COM1_SCHPO] Endonuclease that cooperates with the MRN complex in processing meiotic and mitotic double-strand breaks by allowing the endonucleolytic removal of rec12 from the break sites and ensuring both resection and intrachromosomal association of the broken ends. Required for the formation of RPA-coated single strand DNA adjacent to the DSBs where it functions together with the MRN complex in 5'- 3' resection. Required for the repair of programmed meiotic DSBs. Involved also in an rhp51 recombinase-dependent recombinational repair pathway.[1] [2] [3] [4] Publication Abstract from PubMedCtp1 (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. Tetrameric Ctp1 coordinates DNA binding and DNA bridging in DNA double-strand-break repair.,Andres SN, Appel CD, Westmoreland JW, Williams JS, Nguyen Y, Robertson PD, Resnick MA, Williams RS Nat Struct Mol Biol. 2015 Jan 12. doi: 10.1038/nsmb.2945. PMID:25580577[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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