Michael George Kemp, Ph.D. (Advisor); Jeffrey B. Travers, M.D., Ph.D. (Committee Member); Ji C. Bihl, M.D., Ph.D. (Committee Member)
Master of Science (MS)
Ultraviolet (UV) radiation induces the formation of cyclobutane pyrimidine dimers (CPDs) in genomic DNA, which are normally removed by nucleotide excision repair. However, the fate of these adducts remain largely unexplored. Detection of these photoproducts in body fluids could act as a predictor of UV exposure and enable a better understanding of the pathogenesis of photosensitive skin diseases, such as lupus. Using cultured human keratinocytes exposed to UVB radiation in vitro, ultracentrifugation of cell culture supernatants, and immunodot blot analysis of isolated DNA, we have found that a small fraction of CPDs is released from cells in a dose- and time-dependent manner in association with small extracellular vesicles (SEVs). Furthermore, pharmacological manipulation of cell signaling pathways revealed that caspase-dependent apoptotic signaling was critical to the release of SEVs containing CPDs. These results show for the first time that CPDs are released from UVB-irradiated cells and co-purify with SEVs.
Department or Program
Department of Neuroscience, Cell Biology, and Physiology
Year Degree Awarded
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