| Structural highlights
Function
[NBS1_SCHPO] Required for DNA damage repair and S-phase DNA damage checkpoint. Involved in telomere length maintenance and maintenance of chromatin structure.[1] [2] [CTP1_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.[3] [4] [5] [6]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The Nijmegen breakage syndrome 1 (Nbs1) subunit of the Mre11-Rad50-Nbs1 (MRN) complex protects genome integrity by coordinating double-strand break (DSB) repair and checkpoint signaling through undefined interactions with ATM, MDC1, and Sae2/Ctp1/CtIP. Here, fission yeast and human Nbs1 structures defined by X-ray crystallography and small angle X-ray scattering (SAXS) reveal Nbs1 cardinal features: fused, extended, FHA-BRCT(1)-BRCT(2) domains flexibly linked to C-terminal Mre11- and ATM-binding motifs. Genetic, biochemical, and structural analyses of an Nbs1-Ctp1 complex show Nbs1 recruits phosphorylated Ctp1 to DSBs via binding of the Nbs1 FHA domain to a Ctp1 pThr-Asp motif. Nbs1 structures further identify an extensive FHA-BRCT interface, a bipartite MDC1-binding scaffold, an extended conformational switch, and the molecular consequences associated with cancer predisposing Nijmegen breakage syndrome mutations. Tethering of Ctp1 to a flexible Nbs1 arm suggests a mechanism for restricting DNA end processing and homologous recombination activities of Sae2/Ctp1/CtIP to the immediate vicinity of DSBs.
Nbs1 flexibly tethers Ctp1 and Mre11-Rad50 to coordinate DNA double-strand break processing and repair.,Williams RS, Dodson GE, Limbo O, Yamada Y, Williams JS, Guenther G, Classen S, Glover JN, Iwasaki H, Russell P, Tainer JA Cell. 2009 Oct 2;139(1):87-99. PMID:19804755[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ueno M, Nakazaki T, Akamatsu Y, Watanabe K, Tomita K, Lindsay HD, Shinagawa H, Iwasaki H. Molecular characterization of the Schizosaccharomyces pombe nbs1+ gene involved in DNA repair and telomere maintenance. Mol Cell Biol. 2003 Sep;23(18):6553-63. PMID:12944481
- ↑ Chahwan C, Nakamura TM, Sivakumar S, Russell P, Rhind N. The fission yeast Rad32 (Mre11)-Rad50-Nbs1 complex is required for the S-phase DNA damage checkpoint. Mol Cell Biol. 2003 Sep;23(18):6564-73. PMID:12944482
- ↑ 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
- ↑ Williams RS, Dodson GE, Limbo O, Yamada Y, Williams JS, Guenther G, Classen S, Glover JN, Iwasaki H, Russell P, Tainer JA. Nbs1 flexibly tethers Ctp1 and Mre11-Rad50 to coordinate DNA double-strand break processing and repair. Cell. 2009 Oct 2;139(1):87-99. PMID:19804755 doi:10.1016/j.cell.2009.07.033
|
