Date of Graduation

Spring 2025

Degree

Master of Science in Biomedical Sciences

Department

School of Heath Sciences

Committee Chair

Joshua J Smith

Abstract

In 2020, 10 million deaths were attributed to cancer, with multidrug resistance being responsible for over 90% of deaths in cancer patients receiving treatment. This study utilized the model organism Tetrahymena thermophila to study how cells become resistant to Ultraviolet Radiation (UV) radiation, a process similar to multidrug resistance, specifically focusing on the nucleotide excision repair and ubiquitin shuttle protein Rad23. The National Cancer Institute documented 30-60% of cancers tested had a mutation in RAD23. Knockdown of RAD23 in Tetrahymena thermophila demonstrated a UV resistance phenotype with decreased nucleotide excision repair and differential expression of proteins active within caspase-independent cell death instigated by mitochondrial outer membrane permeabilization and radical oxygen species release. This study concluded that Rad23 has an essential role within caspase-independent cell death leading to UV resistance. This study uncovers a potential role for Rad23 in caspase independent cell death and opens up the ability to use Tetrahymena thermophila as a model organism in which to study how cancer cells utilize caspase-independent cell death to become multidrug resistant.

Keywords

DNA damage, DNA repair, Tetrahymena thermophila, nucleotide excision repair, Rad23, cancer, caspase independent cell death, reactive oxygen species, mitochondria

Subject Categories

Cancer Biology | Cell Biology | Genetic Phenomena | Genetic Processes | Medical Cell Biology | Medical Genetics | Medical Molecular Biology | Neoplasms

Copyright

© Emma June Liimatta

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