Interrogation of telomerase structure and function with telomeric DNA Public Deposited

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  • March 21, 2019
Creator
  • Moon, Ian K.
    • Affiliation: Eshelman School of Pharmacy, Division of Chemical Biology and Medicinal Chemistry
Abstract
  • The studies described in this dissertation are directed toward understanding one of the components of a mechanism that cancer cells use to escape apoptosis and maintain genetic stability, resulting in cellular immortalization. Telomeres are nucleoprotein structures at the ends of eukaryotic chromosomes that are essential for safeguarding genomic stability and in regulating the lifespan of cellular replication. Telomerase is a specialized ribonucleoprotein complex that functions as a reverse transcriptase to extend the 3' end of the telomere, resulting in telomere conservation, and thus chromosomal stabilization. In greater than 85% of all cancer cells, telomerase is upregulated to rescue eroded telomeres and stabilize chromosomes, resulting in cellular immortalization. Because most somatic cells do not express detectable levels of telomerase, telomere-telomerase interactions are important in understanding cellular immortalization and aging, and developing specific anti-cancer therapeutics. Despite the great interest in telomerase, the mechanism of telomerase-catalyzed reverse transcription is not fully understood, and little is known about the structure of this intriguing enzyme. Each chapter, herein, describes novel research that investigates telomerase oligomerization and interactions between telomerase and model telomeric structures. More specifically, Chapter II focuses on the characterization and visualization of cooperative Euplotes aedicualtus telomerase dimers by gel filtration chromatography and electron microscopy. Chapter III details the formation, isolation, and characterization of G-quadruplex DNA structures by native gel electrophoresis, while Chapter IV documents novel interactions between a subset of G-quadruplex DNA structures and Euplotes aediculatus telomerase. Chapter V concludes the dissertation with a retrospective analysis of the research herein.
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  • Jarstfer, Michael
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