4x01

From Proteopedia

(Difference between revisions)

Current revision

S. pombe Ctp1 tetramerization domain

Structural highlights

4x01 is a 8 chain structure with sequence from Schizosaccharomyces pombe 972h-. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.201Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4x01"

Categories: Large Structures | Schizosaccharomyces pombe 972h- | Andres SN | Williams RS

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 4x01 is ON HOLD
+==S. pombe Ctp1 tetramerization domain==
+<StructureSection load='4x01' size='340' side='right'caption='[[4x01]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4x01]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Schizosaccharomyces_pombe_972h- Schizosaccharomyces pombe 972h-]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4X01 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4X01 FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.201&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4x01 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4x01 OCA], [https://pdbe.org/4x01 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4x01 RCSB], [https://www.ebi.ac.uk/pdbsum/4x01 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4x01 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/COM1_SCHPO 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.<ref>PMID:16303567</ref> <ref>PMID:17936710</ref> <ref>PMID:18378696</ref> <ref>PMID:19139281</ref>
+<div style="background-color:#fffaf0;">
+== 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.
-Authors: Andres, S.N. , Williams, R.S.
+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<ref>PMID:25580577</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 4x01" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Schizosaccharomyces pombe 972h-]]
+[[Category: Andres SN]]
+[[Category: Williams RS]]

4x01

From Proteopedia

Current revision

S. pombe Ctp1 tetramerization domain

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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