Principal Investigator Stephen Bell
Replication of the eukaryotic genome is restricted to the S phase of the cell cycle. Within S phase, each origin of replication initiates replication at a characteristic time. This temporal regulation of initiation is a conserved feature of all eukaryotic genomes, yet we know little about either how or why origin initiation is temporally regulated. We are taking multiple approaches to understand the mechanisms that regulate origin usage in S. cerevisiae. First, we have used both computational and genomic approaches to map origins across the yeast genome at nucleotide resolution. These data have allowed us to perform precise sequence comparisons between different classes of origins (e.g. early and late) revealing previously uncharacterized sequence differences. In addition, we have developed genetic screens to identify genes that influence the time of origin initiation within S phase in the yeast S. cerevisiae. We are now determining how these genes influence the time of initiation with the long-term goal of understanding the cellular importance of maintaining the correct temporal pattern of replication.