DNA复制是所有生物最基本的生物学过程，而寻找参与复制的新的蛋白因子是DNA复制研究主要课题之一。古菌是生物界三域之一，其DNA复制蛋白更接近于真核生物而成分相对简单，同时古菌复制机制又有其独特的特征。申请人前期利用质谱分析方法构建了超嗜热古菌Thermococcus DNA复制网络，其中包含50余种新型蛋白。同时，申请人已证实其中两种蛋白GAN和TIP参与古菌DNA复制。该网络中有一个蛋白TK1046与包括DNA聚合酶在内的多个已知DNA复制蛋白存在相互作用。有趣的是该蛋白拥有保守的核酸结合结构域（OB-fold），推测其很可能是一个参与DNA复制的全新蛋白。本课题计划利用分子生物学、生物化学和遗传学等研究方法，研究TK1046及其同源蛋白的性质和功能，该新型DNA复制蛋白的鉴定和分析预期将加深我们对古菌乃至真核生物DNA复制机制及其进化性质的认识和理解。

The mechanism of DNA replication in archaea, the third domain of life, has been studied for more than two decades using biochemical, structural and bioinformatic approaches. However, comparing with the studies in eukaryote and bacteria, the DNA replication mechanism and proteins in archaea were far less revealed. Using Mass-spectrum, the applicant previously identified a network containing 50 new putative DNA replication proteins from the thermophilic archaea Thermococcus kodakarensis. Two (2) proteins (GAN, GINS Associated Nuclease and TIP, Thermococcales Inhibitor of PCNA) were identified from the above network as new DNA replication proteins. Here the applicant noticed another putative DNA replication protein TK1046, which contained a conserved OB fold. The later was remarkably known as a sign of nucleic acid binding domain and hence strongly indicated the involvement of TK1046 in DNA metabolism. To better understand this new DNA replication factor, a plan was proposed to characterize the biological function of TK1046 using a combination of techniques including biochemistry, biophysics, genetics and molecular biology.