The structural maintenance of chromosomes (SMC) proteins, which are evolutionarily conserved from prokaryotes to eukaryotes, are essential for higher order chromosome organizations and functions. Six members of SMCs have been identified in eukaryotes which form three distinct complexes: cohesin, condensin and the Smc5/6 complex. Each of the SMC complexes has a unique function. Cohesin is responsible for linking sister chromatids during mitosis and meiosis, whereas condensin is required for condensation of chromosomes during mitosis and meiosis. The Smc5/6 holocomplex, formed by a heterodimer of Smc5 and Smc6 in association with six non-SMC components in both Saccharomyces cerevisiae and Schizosaccharomyces pombe, is localized on repetitive rDNA and telomere, and is important for DNA replication and double stranded DNA damage repair through homologous recombination. SMC proteins are organized into five domains: an N-terminal head domain, a long coiled-coil helix, a hinge domain, another long coiled-coil helix and a C-terminal head domain. The N- and C-terminal head domains associate together to form an ATPase head domain. The long coiled-coil helices associate together to form the coiled-coil arm. The hinge domain dimerizes to form the hinge of the complex. While the head appears to recognize DNA, the hinge controls the spatial topology of the arms and the head and therefore the conformation of overall structure. In the Smc5/6 holocomplex, the non-SMC component Mms21, a SUMO E3 ligase, is important for Smc5/6-mediated DNA damage repair. The molecular mechanism of the function is unclear. In addition, limited structural information is available on SMC complexes, especially Smc5/6. To fill this gap, we propose a series of comprehensive studies on several important aspects of this complex, which will have tremendous impact on the molecular basis of Smc5/6 function as well as the functions of cohesin and condensin.
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