Mechanism and Regulation of Chromosome Replication

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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.