Proper progression through the cell cycle is critical for cell growth and survival. Disruption of cell cycle progression can lead to cell cycle arrest and cell death. In addition, uncontrolled cell cycle progression can lead to cancer. Cells have evolved complex mechanisms to regulate each phase of the cell cycle to ensure proper cell cycle progression. In the presence of cellular stress, cells will respond promptly to arrest the cell cycle and allow repair. In order to study this complex process, it is important to identify the complete complement of proteins involved. I took two large-scale approaches to study the cell cycle. First, I down-regulated the majority of essential genes in Saccharomyces cerevisiae, and determined how depletion of individual gene product affected progression through the cell cycle. I determined that over 65% of essential genes I tested are most important at a specific cell cycle phase. In addition, I found that two genes, Smc4 and Cse1, have novel roles in S-phase of the cell cycle. In the second approach, I discovered two anti-proliferative compounds. Both compounds caused cell cycle delay in G1 phase of the cell cycle. Chemical genetic screens in yeast allowed me to determine the pathways most sensitive to each of these two compounds. By studying the response of cells to these compounds, I confirmed that compound 13 causes mitochondrial dysfunction in cells and compound 15 causes nuclear DNA damage. Furthermore, I found that both compounds are toxic in mammalian cells and that the responses that they elicit in mammalian cells are similar to those observed in yeast cells.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OTU.1807/17244 |
| Date | 26 February 2009 |
| Creators | Yu, Lisa |
| Contributors | Brown, Grant |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
| Format | 3388933 bytes, application/pdf |
Page generated in 0.0023 seconds