Doctor of Philosophy (PhD)
First Advisor's Name
Marcus S. Cooke
First Advisor's Committee Title
Second Advisor's Name
Stanislaw F. Wnuk
Second Advisor's Committee Title
Third Advisor's Name
Third Advisor's Committee Title
Fourth Advisor's Name
Fourth Advisor's Committee Title
Fifth Advisor's Name
Fifth Advisor's Committee Title
Sixth Advisor's Name
Sixth Advisor's Committee Title
DNA damage, Environmental exposure, Mitochondiral genomes, nuclear genomes, DNA repair
Date of Defense
All living organisms are continually exposed to various environmental stressors, be they anthropogenic or natural in origin. Many stressors share a common toxic mechanism, generating highly reactive chemical species that can have detrimental effects. A proportion of these chemical species evade the cell’s defenses and damage cellular components, including DNA. Measurement of global genome levels of DNA and cellular damage has implicated environmental stressors in major human health issues (e.g., cancer, aging, cardiovascular, and neurodegenerative diseases). Current associations between DNA damage and disease are based upon crude assessments of global genome damage, which provide limited mechanistic information on how damage leads to disease. Furthermore, DNA damage is not uniformly distributed across the genome; accumulation, or persistence, of damage in regions of the genome vital to the functioning of the cell, will have downstream consequences. Thus, we proposed, that the role of DNA damage in disease can only be understood by examination of damage in the context of its location and damage response during the repair. Currently we lack information concerning how the cell maintains baseline levels of DNA damage and its spatio-temporal distribution across the genome. This is fundamental to our understanding of how the cell responds to damage and whether regions are targeted for prioritized repair. In this study, we have refined a popular method of assessing global DNA damage, to increase the efficiency of the assay, mapped UV-induced T<>T across both nuclear and mitochondrial genomes, and evaluated the changes in the cellular DNA damage response during bacterial infection. The aim of these studies was to evaluate the importance of cellular response to exposure to environmental toxicants.
Previously Published In
Karbaschi, M., Ji, Y., Abdulwahed, A. M. S., Alohaly, A., Bedoya, J. F., Burke, S. L., ... & Cooke, M. S. (2019). Evaluation of the Major Steps in the Conventional Protocol for the Alkaline Comet Assay. International Journal of Molecular Sciences, 20(23), 6072.
Alhegaili, A. S., Ji, Y., Sylvius, N., Blades, M. J., Karbaschi, M., Tempest, H. G, ... & Cooke, M. S. (2019). Genome-Wide Adductomics Analysis Reveals Heterogeneity in the Induction and Loss of Cyclobutane Thymine Dimers across Both the Nuclear and Mitochondrial Genomes. International journal of molecular sciences, 20(20), 5112.
Ji, Y., Karbaschi, M., & Cooke, M. S. (2019). Mycoplasma infection of cultured cells induces oxidative stress and attenuates cellular base excision repair activity. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 845, 403054.
Ji, Yunhee, "Formation and Repair of Environmentally-induced damage to Mitochondrial and Nuclear Genomes" (2020). FIU Electronic Theses and Dissertations. 4585.
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