The SMC5-6 DNA repair complex: Bridging of the SMC5-6 heads by the Kleisin, NSE4, and non-Kleisin subunits
Doherty, A. J.
Lehmann, A. R.
- Publisher: American Society for Biochemistry and Molecular Biology
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.