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Epigenetic Control Mechanisms In Somatic Cells Mediated By Dna Methyltransferase 1, Bongyong Lee
Epigenetic Control Mechanisms In Somatic Cells Mediated By Dna Methyltransferase 1, Bongyong Lee
Electronic Theses and Dissertations
DNA methylation regulates gene expression through a complex network of protein/protein and protein/DNA interactions in chromatin. The maintenance methylase, DNA methyltransferase 1 (DNMT1), is a prominent enzyme in the process that is linked to DNA replication and drives the heritable nature of epigenetic modifications in somatic cells. The mechanistic details that explain how DNMT1 catalytic action is directed in a chromatin setting are not well understood. We hypothesize that post translational modifications and a variety of protein-protein interactions processes are key regulatory elements that set the methylation of CpG elements essential for normal growth behavior in somatic cells. These fundamental …
Impact Of Genetic And Epigenetic Variability In Response To Two Test Drugs 5-Fluorouracil And Lansoprazole, Adam Michael Lee
Impact Of Genetic And Epigenetic Variability In Response To Two Test Drugs 5-Fluorouracil And Lansoprazole, Adam Michael Lee
All ETDs from UAB
Pharmacogenetics has proven to be an invaluable tool in predicting variability in drug response; however, there are numerous incidences where genetics cannot fully explain interindividual drug variability. Other factors, such as the epigenetic mechanism of DNA methylation, may offer an alternate explanation. Therefore, this dissertation focuses on both genetic and epigenetic regulation in order to gain a better understanding of the molecular basis behind drug response variability. Initial investigations focused on the antineoplastic agent 5-Fluorouracil (5-FU), which can produce severe toxicity in patients with deficiency in dihydropyrimidine dehydrogenase (DPD). Genotypic studies have identified >32 sequence variants in the DPYD gene; …