title: The Smc5-Smc6 DNA repair complex. bridging of the Smc5-Smc6 heads by the KLEISIN, Nse4, and non-Kleisin subunits.
abstract: 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-Smc6 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 delta-kleisin subfamily. We further show that Nse3, as well as Nse5 and Nse6, also bridge the heads of Smc5 and -6. The Nse1-Nse3-Nse4 and Nse5-Nse6 subcomplexes bind to the Smc5-Smc6 heads domain at different sites.
authors.affiliation: Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RQ, United Kingdom.
authors.forename: Jan
authors.initials: J
authors.lastname: Palecek
authors.forename: Susanne
authors.initials: S
authors.lastname: Vidot
authors.forename: Min
authors.initials: M
authors.lastname: Feng
authors.forename: Aidan J
authors.initials: AJ
authors.lastname: Doherty
authors.forename: Alan R
authors.initials: AR
authors.lastname: Lehmann
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000502:physiology*; D004260:DNA Repair; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D020798:Two-Hybrid System Techniques
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C493528:Nse4 protein, S pombe; D016271:Proto-Oncogene Proteins c-myc; D029702:Schizosaccharomyces pombe Proteins; C486628:Smc5 protein, S pombe; C486630:smc6 protein, S pombe