Date of Award

Spring 5-2019

Degree Type

Thesis

Department

Biological Sciences

Director of Thesis

Dr. Douglas L. Pittman

First Reader

Dr. Holly Crocker

Second Reader

Dr. Holly Crocker

Abstract

Ovarian cancers are the leading cause of death from cancer of the female reproductive system. Approximately 50% of ovarian cancers have defects in the homologous recombination (HR) DNA repair pathway that is required for the repair of DNA double-stranded breaks. The status of HR genes, such as BRCA1, BRCA2, and the RAD51 family, contributes to ovarian cancer development as well as treatment decisions regarding chemotherapy, radiation, and immunotherapy. The overarching goal of this project is to identify new insights into HR that can integrate with Precision Medicine Initiatives and align with the goals of the Cancer Moonshot 2020 Program. I have hypothesized that specific RAD51D mutations disrupt RAD51D cellular localization since the absence of RAD51D from the nucleus is expected to increase DNA damage and chromosome instability. Mutant constructs were generated and fused to the Green Fluorescent Protein (GFP) gene so that fluorescent localization studies of RAD51D could be conducted. The data were quantified to determined if the protein constructs were localized to the nucleus or the cytoplasm. In this paper, the lysine to arginine mutant K298R was analyzed and compared to RAD51D WT. Current data suggest that RAD51D-K298R appears to have a statistically significant decrease of GFP expression in the cytoplasm compared to WT. In future experimentation, transfected cells will be treated with DNA crosslinking agents to determine the affect on RAD51D localization. If the mutated regions along the RAD51D protein alter localization in either the cytoplasm or nucleus, they can provide a potential target site to block RAD51D function and sensitize or re-sensitize cells to chemotherapeutic agents.

With my cross-disciplinary art project, I want to spread awareness and understanding of how the genetics of ovarian cancer works as it is the fifth most prevalent cancer amongst women and, according to the American Cancer Society, women have a one in seventy-five chance of being diagnosed with ovarian cancer during their lifetime. I want to engage people in scientific research whom may not be otherwise interested in it; to show others that there can be beauty in laboratory research work and that it is not just pipetting and statistics. When examined closely, we can see the universe everywhere, even under a microscope. Each piece in my work has been named after historical or contemporary female scientists who I find extremely fascinating or have influenced me personally. I chose to do this not only to represent women in science but also to represent the female population that is heavily impacted by ovarian cancer.

First Page

1

Last Page

39

Rights

© 2019, Claire L Chabot

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