| 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 PubMed
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.
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
- ↑ Martin-Castellanos C, Blanco M, Rozalen AE, Perez-Hidalgo L, Garcia AI, Conde F, Mata J, Ellermeier C, Davis L, San-Segundo P, Smith GR, Moreno S. A large-scale screen in S. pombe identifies seven novel genes required for critical meiotic events. Curr Biol. 2005 Nov 22;15(22):2056-62. PMID:16303567 doi:http://dx.doi.org/S0960-9822(05)01277-7
- ↑ Limbo O, Chahwan C, Yamada Y, de Bruin RA, Wittenberg C, Russell P. Ctp1 is a cell-cycle-regulated protein that functions with Mre11 complex to control double-strand break repair by homologous recombination. Mol Cell. 2007 Oct 12;28(1):134-46. PMID:17936710 doi:http://dx.doi.org/10.1016/j.molcel.2007.09.009
- ↑ Akamatsu Y, Murayama Y, Yamada T, Nakazaki T, Tsutsui Y, Ohta K, Iwasaki H. Molecular characterization of the role of the Schizosaccharomyces pombe nip1+/ctp1+ gene in DNA double-strand break repair in association with the Mre11-Rad50-Nbs1 complex. Mol Cell Biol. 2008 Jun;28(11):3639-51. doi: 10.1128/MCB.01828-07. Epub 2008 Mar , 31. PMID:18378696 doi:http://dx.doi.org/10.1128/MCB.01828-07
- ↑ Hartsuiker E, Mizuno K, Molnar M, Kohli J, Ohta K, Carr AM. Ctp1CtIP and Rad32Mre11 nuclease activity are required for Rec12Spo11 removal, but Rec12Spo11 removal is dispensable for other MRN-dependent meiotic functions. Mol Cell Biol. 2009 Apr;29(7):1671-81. doi: 10.1128/MCB.01182-08. Epub 2009 Jan, 12. PMID:19139281 doi:http://dx.doi.org/10.1128/MCB.01182-08
- ↑ Andres SN, Appel CD, Westmoreland JW, Williams JS, Nguyen Y, Robertson PD, Resnick MA, Williams RS. Tetrameric Ctp1 coordinates DNA binding and DNA bridging in DNA double-strand-break repair. Nat Struct Mol Biol. 2015 Jan 12. doi: 10.1038/nsmb.2945. PMID:25580577 doi:http://dx.doi.org/10.1038/nsmb.2945
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