Mechanism and Regulation of Chromosome Replication

生命始于一个单细胞，然后这个单细胞必须经过多次分裂才能产生数万亿个细胞，这些细胞构成了像人类这样的复杂有机体。在每一次分裂之前，人类细胞必须对组成个体基因蓝图的46条染色体中的每一条染色体都进行完整的、新的复制。染色体复制过程中的任何错误都会威胁到这一蓝图，并可能导致人类疾病，如癌症和各种发育障碍。因此，提高对染色体复制的机制和调控的理解是必不可少的。我的实验室研究控制染色体复制的分子机器，称为复制体。为了全面了解这台机器，我们在试管中从单个蛋白质成分中构建了复制体，并研究了它的分子机制和调控。我们对染色体复制的最后阶段特别感兴趣，包括染色体复制完成后，复制体是如何分离的。最终，我们的工作将提供细胞如何正常复制染色体的详细图片，以及这个过程如何在癌症等疾病中出错。这项工作将有助于我们了解许多人类疾病的分子起源，并具有相当大的潜力，为开发针对染色体复制机制的新疗法提供新的机会。

Life begins as a single cell, which must then divide many times to produce the trillions of cells that make up complex organisms such as humans. Before every division, a human cell must make a complete, new copy of every one of the 46 chromosomes that together make up an individual’s genetic blueprint. Any errors made during chromosome replication threaten this blueprint, and can cause human diseases such as cancer and various developmental disorders. An improved understanding of the mechanism and regulation of chromosome replication is therefore essential.My lab studies the molecular machine that controls chromosome replication, called the replisome. To develop a comprehensive understanding of this machine, we build the replisome in a test tube from individual protein components, and investigate it’s molecular mechanisms and regulation. We are particularly interested in the poorly understood final stages of chromosome replication, including how the replisome is taken apart when chromosome replication has been completed.Ultimately, our work will provide a detailed picture of how cells replicate their chromosomes normally, and how this process goes wrong in diseases such as cancer. This work will contribute towards our understanding of the molecular origins of numerous human diseases, and has considerable potential to provide new opportunities for the development of novel therapies that target the chromosome replication machinery.