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Structure of the S. pombe Nbs1 FHA/BRCT-repeat domain
Structural highlights
FunctionNBS1_SCHPO Required for DNA damage repair and S-phase DNA damage checkpoint. Involved in telomere length maintenance and maintenance of chromatin structure.[1] [2] 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 PubMedThe Mre11/Rad50/Nbs1 protein complex plays central enzymatic and signaling roles in the DNA-damage response. Nuclease (Mre11) and scaffolding (Rad50) components of MRN have been extensively characterized, but the molecular basis of Nbs1 function has remained elusive. Here, we present a 2.3A crystal structure of the N-terminal region of fission yeast Nbs1, revealing an unusual but conserved architecture in which the FHA- and BRCT-repeat domains structurally coalesce. We demonstrate that diphosphorylated pSer-Asp-pThr-Asp motifs, recently identified as multicopy docking sites within Mdc1, are evolutionarily conserved Nbs1 binding targets. Furthermore, we show that similar phosphomotifs within Ctp1, the fission yeast ortholog of human CtIP, promote interactions with the Nbs1 FHA domain that are necessary for Ctp1-dependent resistance to DNA damage. Finally, we establish that human Nbs1 interactions with Mdc1 occur through both its FHA- and BRCT-repeat domains, suggesting how their structural and functional interdependence underpins Nbs1 adaptor functions in the DNA-damage response. A supramodular FHA/BRCT-repeat architecture mediates Nbs1 adaptor function in response to DNA damage.,Lloyd J, Chapman JR, Clapperton JA, Haire LF, Hartsuiker E, Li J, Carr AM, Jackson SP, Smerdon SJ Cell. 2009 Oct 2;139(1):100-11. PMID:19804756[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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