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Title page for ETD etd-03252013-232921

Type of Document Dissertation
Author Ferguson, Jenifer Lynn
URN etd-03252013-232921
Title Exploring the Cell Cycle-Regulated Degradation of the Saccharomyces cerevisiae Telomerase Recruitment Subunit Est1
Degree PhD
Department Biological Sciences
Advisory Committee
Advisor Name Title
Todd Graham Committee Chair
James Patton Committee Member
Katherine Friedman Committee Member
Kathleen Gould Committee Member
Laura Lee Committee Member
  • Telomerase
  • Protein Degradation
  • Anaphase Promoting Complex
Date of Defense 2013-02-26
Availability unrestricted
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.
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