Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

For accurate cell division to occur, a cell must both replicate its DNA (chromosomes) accurately and then separate it equally to the two resultant cells, a process that is termed mitosis. If there are any errors in these events, a cell may inherit an abnormal amount of genetic information, which can lead to a number of diseases including Down's Syndrome and cancer. Therefore, to monitor this critical process, a cell employs a series of quality control mechanisms, or "checkpoints", throughout cell division. Should a mistake in DNA replication or mitosis occur, these checkpoints will be triggered, preventing cell division from continuing until the error is corrected. An important example of this is the aptly termed DNA Replication Checkpoint (DRC), which monitors the successful replication of chromosomal DNA. Our lab uses budding yeast to study how accurate chromosomal separation is achieved because of the high conservation of proteins required for chromosome separation. By using this simple organism as a model, we may be able to extrapolate how these cellular mechanisms occur in higher species, such as humans. Once chromosomes are replicated, they are paired with their newly duplicated chromosome, or sister chromatid. In order to be separated, a protein known as Esp1 comes in to cleave the "molecular glue" holding them together. Though Esp1 is a well described protein, I have recently found that it may have a function at the DRC. This is because a mutant form of it was unable to grow when the DRC was triggered using Hydroxyurea (HU), a drug that stalls DNA replication. The aim of my research project is to search for candidate Esp1 substrates and to use a genome wide approach to study the biological role of Esp1 during the DRC. My long term goal is to better understand how a cell is able to pass on its genetic material successfully when it undergoes cell division.