The SMC5-6 DNA repair complex: Bridging of the SMC5-6 heads by the Kleisin, NSE4, and non-Kleisin subunits

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Palecek, J. ; Vidot, S. ; Feng, M. ; Doherty, A. J. ; Lehmann, A. R. (2006)
  • Publisher: American Society for Biochemistry and Molecular Biology
  • Related identifiers: doi: 10.1074/jbc.M608004200
  • Subject: QD | QH301

Structural Maintenance of Chromosomes (SMC) proteins play fundamental roles in many aspects of chromosome organization and dynamics. The SMC complexes form unique structures with long coiled-coil arms folded at a hinge domain, so that the globular N- and C-terminal domains are brought together to form a "head". Within the Smc5/6 complex, we previously identified two subcomplexes containing Smc6-Smc5-Nse2 and Nse1-Nse3-Nse4. A third subcomplex containing Nse5 and 6 has also been identified recently. We present evidence that Nse4 is the kleisin component of the complex, which bridges the heads of Smc5 and 6. The C-terminal part of Nse4 interacts with the head domain of Smc5 and structural predictions for Nse4 proteins suggest similar motifs that are shared within the kleisin family. Specific mutations within a predicted winged helix motif of Nse4 destroy the interaction with Smc5. We propose that Nse4 and its orthologs form the d-kleisin subfamily. We further show that Nse3, as well as Nse5 and Nse6 also bridge the heads of Smc5 and 6. The Nse1-3-4 and Nse5-6 subcomplexes bind to the Smc5-6 heads domain at different sites.
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    Scc1 --------GPLAQIWLASNMS---NIPRGSV--IQTHIAESAKEIAKASG-[8]-EYITLRTSGELLQGIVRVYSKQATFL B.s. --------GPLDLLLHLINRL---EIDIYDIP--VAKITEQYLLYVHTMR------VLELDIASEYLVMAATLLSIKSRML

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