The Role of rad51c on the Fanconi Anemia Pathway in Zebrafish
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Date
2017
Authors
Carroll, Victoria Marie
Journal Title
Journal ISSN
Volume Title
Publisher
University of Oregon
Abstract
DNA is exposed to various forms of damage from both natural and anthropogenic causes. Normal cells repair this damage, which allows them to remain viable. However, cells with mutations in DNA repair genes are unable to repair the damage, which leads to cancers and/or cell death. My research examined RAD51C, a gene involved in DNA repair by homologous recombination. Homologous recombination repairs a form of DNA damage known as double strand breaks in which both strands of DNA are severed. Mutations in RAD51C lead to breast and ovarian cancer in humans and, as of 2010, were thought to be related to Fanconi anemia (FA), but evidence was based on a single patient whose symptoms did not conform to the classical phenotype of FA. FA is a rare autosomal disorder characterized by chromosome instability, progressive bone marrow failure, developmental abnormalities, and a predisposition to cancer. The goal of my research was to provide firm evidence whether mutations in RAD51C mimic FA symptoms. In zebrafish, FA involves female-to-male sex reversal, reduced fertility, and sensitivity to DNA crosslinking agents. I analyzed the effects of the rad51c mutation in zebrafish with respect to sex determination, fertility, early hematopoietic gene expression, and the ability of cells to respond to DNA damage. My results showed that rad51c mutations in zebrafish do mimic the symptoms of bona fide zebrafish FA mutants and thus verify the designation of rad51c as an FA gene. This research will lead to a better understanding of the role of rad51c in human health, and will ultimately improve detection, prevention, and therapies for cancer and Fanconi anemia.
Description
46 pages. A thesis presented to the Department of General Science and the Clark Honors College of the University of Oregon in partial fulfillment of the requirements for degree of Bachelor of Science, Spring 2017
Keywords
Fanconi Anemia, Rad51C, Homologous Recombination, DNA Repair, Zebrafish, Breast Cancer