My laboratory studies how the human genome is replicated. Every time one of our cells divides, billions of DNA base pairs must be copied accurately and in the correct order. This process must also be carefully coordinated with other essential activities in the nucleus, including gene expression and DNA repair. To ensure that the genome is completely and faithfully duplicated during each cell division, cells rely on complex regulatory systems that determine when and where different regions of the genome are copied. We are only beginning to understand the mechanisms that govern this “replication program.” However, it is already clear that disruptions in DNA replication control can lead to cancer, age-related diseases, and birth defects. By defining the fundamental principles and specific mechanisms that regulate DNA replication, we aim to lay the groundwork for improved treatments for a range of human diseases, including cancer.
To gain both detailed mechanistic insight and in vivo understanding, we study DNA replication in cultured human cells and in zebrafish embryos. Because zebrafish embryos develop externally and undergo rapid, synchronized cell divisions, they provide a powerful system for understanding how the genome is accurately replicated during embryonic development. Zebrafish also allow genetic experiments to be performed more quickly and efficiently than in many other vertebrate models.
Our current research focuses on the core mechanisms that control DNA replication during normal cell division and on how cells adjust replication in response to developmental changes and cellular stress. We study several replication control genes that are conserved across vertebrates, from fish to humans. In particular, we focus on TICRR (also known as TRESLIN), a replication control gene we identified in a zebrafish genetic screen. We have shown that TICRR/TRESLIN is a critical component of the system that determines when and where DNA replication begins across the genome.