The work presented in this dissertation focuses on the temporal regulation of telomerase complex assembly in the yeast Saccharomyces cerevisiae as mediated by protein degradation of a core subunit during G1 phase of the cell cycle. I have discovered that the Est1 protein undergoes rapid degradation only during G1 phase of the cell cycle and that degradation requires function of the Anaphase Promoting Complex (APC), an E3 ubiquitin ligase. Furthermore, release of cells through G1 phase shows that Est1 protein degradation depends upon the APC activator protein Cdh1. Mutational analysis revealed specific amino acids of the Est1 protein that are necessary for degradation. Despite strong evidence for a role of the APC in Est1p stability in vivo, recombinant Est1 protein is not degraded or ubiquitinated in vitro using several different assays. These studies suggest that stability of the Est1 protein in vivo may be indirectly influenced by APC function.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-03252013-232921 |
| Date | 15 April 2013 |
| Creators | Ferguson, Jenifer Lynn |
| Contributors | Todd Graham, James Patton, Kathleen Gould, Laura Lee, Katherine Friedman |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-03252013-232921/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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