真核DNA的复制被严格控制以确保在每个细胞周期中只发生一次。在M和G1期，起始识别复合物（Orc1-6）结合新合成的复制源DNA，募集细胞分裂周期蛋白6（Cdc6）、细胞分裂周期蛋白（Cdt1）以及微小染色体维持蛋白复合物（Mcm2-7），完成前复制复合体（pre-RC）的组装以待开启DNA复制。pre-RC组成蛋白的突变与癌症发生密切相关。特别是在鼻咽癌细胞中，EB病毒利用人的pre-RC与EB 核抗原1 （EBNA1）结合进行其DNA复制。但这些作用的分子机理尚不清楚。以本研究组大量的初始研究结果为基础，通过核磁共振方法、冷冻电镜技术及生化试验，我们将继续深入研究人类正常细胞和鼻咽癌细胞的DNA复制中前复制复合体的结构与功能。此项研究的结果将会极大加深我们对人体DNA复制分子机理的认知，并为抗鼻咽癌药物的设计提供必要的分子结构基础与功能信息。

In order to maintain genetic integrity, the initiation of eukaryotic DNA replication is strictly controlled to warrant that the DNA replication occurs exactly once in each cell cycle. Replication begins by the formation of pre-replicative complexes (pre-RCs) on replication origins during M and G1 phases. For pre-RC assembly, the six-subunit origin recognition complex (ORC) first binds to replication origin on newly synthesized chromatin. ORC serves as an origin marker and recruits the initiation factors, Cdc6 and Cdt1 to origins for the chromatin loading of the hetero hexameric Mcm2-7 complex. Once Mcm2-7 complex is loaded onto chromatin and pre-RC is formed, the cell is licensed for DNA replication, awaiting additional signals for the activation of the licensed origins. The components of pre-RC are strongly coupled with the cancer. Particularly, pre-RC is known to be recruited for latent EBV DNA replication in NPC cells. Based on large amount of the initial results obtained by our research group, we will go on further to study the structure and function studies of pre replication complex in DNA replication of human and NPC cells by applying NMR method, cryo-EM, biochemical and biological techniques. The results of this study will deepen our understanding of the molecular mechanisms of DNA replication, and provide structural and functional insights for drug design and treatment of NPC.