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. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM079516-01A1
Application #
7319519
Study Section
Macromolecular Structure and Function C Study Section (MSFC)
Program Officer
Preusch, Peter C
Project Start
2007-07-01
Project End
2012-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
1
Fiscal Year
2007
Total Cost
$265,023
Indirect Cost
Name
University of Louisville
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
057588857
City
Louisville
State
KY
Country
United States
Zip Code
40292
Duan, Xinyuan; Holmes, William B; Ye, Hong (2011) Interaction mapping between Saccharomyces cerevisiae Smc5 and SUMO E3 ligase Mms21. Biochemistry 50:10182-8
Duan, Xinyuan; Trent, John O; Ye, Hong (2009) Targeting the SUMO E2 conjugating enzyme Ubc9 interaction for anti-cancer drug design. Anticancer Agents Med Chem 9:51-4
Duan, Xinyuan; Ye, Hong (2009) Purification, crystallization and preliminary X-ray crystallographic studies of the complex between Smc5 and the SUMO E3 ligase Mms21. Acta Crystallogr Sect F Struct Biol Cryst Commun 65:849-52
Duan, Xinyuan; Yang, Yan; Chen, Yu-Hung et al. (2009) Architecture of the Smc5/6 Complex of Saccharomyces cerevisiae Reveals a Unique Interaction between the Nse5-6 Subcomplex and the Hinge Regions of Smc5 and Smc6. J Biol Chem 284:8507-15
Chen, Yu-Hung; Choi, Koyi; Szakal, Barnabas et al. (2009) Interplay between the Smc5/6 complex and the Mph1 helicase in recombinational repair. Proc Natl Acad Sci U S A 106:21252-7
Duan, Xinyuan; Sarangi, Prabha; Liu, Xianpeng et al. (2009) Structural and functional insights into the roles of the Mms21 subunit of the Smc5/6 complex. Mol Cell 35:657-68