Formation and Repair of Environmentally-induced damage to Mitochondrial and Nuclear Genomes

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\u3c\u3eT 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