Advisory Committee Chair
David A Schneider
Advisory Committee Members
Maaike Everts
Natalia Kedishvili
Susan Bellis
Document Type
Dissertation
Date of Award
2020
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
My graduate research has focused on understanding the elongation kinetics of RNA polymerase I (Pol I), the enzyme responsible for synthesizing ribosomal RNA (rRNA), and defining how inhibition of ribosome biogenesis may be used as a cancer therapeutic strategy. Here, I have defined key biophysical features of Pol I and I have expanded the field’s understanding of Pol I elongation by: 1) characterizing the enzymatic properties of Pol I by mutational analysis of the polymerase itself, and by 2) elucidating the role of DNA sequence on Pol I arrest and nucleolytic cleavage activity. In recent years, Pol I has become an attractive target for cancer therapeutics, as enhanced ribosome biogenesis is necessary for the rapid growth and proliferation of cancer cells. I have demonstrated that ribosome biogenesis inhibition by a novel inhibitor, RBI2 (ribosome biogenesis inhibitor 2) specifically decreases cancer cell growth and proliferation, likely by increasing premature rRNA turnover. Collectively, my studies on Pol I’s enzymatic properties have resulted in a better understanding of the relationship between cancer cell growth and ribosome biogenesis. As a whole, my thesis research has resulted in a more detailed understanding of RNA polymerase I (Pol I) elongation kinetics and it has further validated inhibition of ribosome biogenesis as a promising cancer chemotherapeutic target.
Recommended Citation
Scull, Catherine Elizabeth, "Rna Polymerase I Elongation Kinetics: A Biochemical And Global Study Of A Cancer Therapeutic Target" (2020). All ETDs from UAB. 2934.
https://digitalcommons.library.uab.edu/etd-collection/2934