染色体结构维持蛋白Smc5/6复合体在真核生物中分布广泛且高度保守，在DNA损伤同源重组修复、DNA复制、端粒长度维持及胚胎发育中都发挥了重要的作用，但是目前对于Smc5/6复合体的功能研究尚处于早期阶段，已知组成蛋白的具体功能和发现新的复合体相关蛋白都有待于进一步的探索。申请人利用正向遗传筛选的方法获得了对DNA损伤敏感的nse-1线虫突变体，其对DNA损伤引起的细胞周期停滞调控缺陷。进一步利用gfp::nse-1转基因线虫的Pulldown和质谱分析不仅获得了包括Smc-5、Smc-6、Nse-2和Nse-4在内的Smc5/6复合体组成蛋白，而且首次发现了Ubl-1蛋白，体外生化分析表明与Nse-1蛋白具有直接相互作用。本课题将利用基因敲除、转基因线虫、RNAi文库和蛋白质组学等手段对Nse-1如何参与基因组稳定性和细胞周期调控的进行深入的研究，阐明Smc5/6复合体作用的分子机理。

The structural maintenance of chromosomes(Smc) 5/6 complex is widely distributed and highly conserved in eukaryotes, and plays an important role in homologous recombination in DNA damage, DNA replication, telomere length maintenance and embryo development. However, the cellular functions of the Smc5/6 complex are relatively poorly understood, and the detailed functions of the constituent proteins and the discovery of new proteins in the Smc5/6 complex are yet to be further explored. The nse1 homolog in Caenorhabditis elegans was identified from a forward genetic screening for new genes involved in DNA damage repair. The nse-1 mutant is defect in regulation of cell cycle arrest caused by DNA damage. Furthermore, the proteins including Smc-5, Smc-6, Nse-2 and Nse-4 were identified in the pull-down assay using the gfp::nse-1 transgenic worm, and Ubl-1 is discovered to be associated with Smc5/6 complex for the first time. It was found that Ubl-1 directly interacted with Nse-1 in vitro. In this project, the molecular mechanism of nse-1 in genomic stability maintenance and cell cycle arrest regulation will be investigated using gene knockout and transgenic worms as well as RNAi library and proteomics. The expected results will provide a firm theoretical foundation for the understanding of Smc-5/6 complex.