Date of Award
John J.H. Hudson
DNA Methylation, Epigenetics, Kinase, Phosphorylation, PLK4
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PLK4 is a serine/threonine kinase known to be involved in cell cycle regulation and centrosome duplication. Its protein levels are tightly regulated in order to prevent centrosome irregularities that would lead to aneuploidy and eventual oncogenesis. Previous studies have shown that PLK4 is under epigenetic control and could also be involved in regulating epigenetic mechanisms. In this study, centrinone-B (a PLK4 inhibitor) was used to determine the functional mechanisms of PLK4 in epigenetic regulation. We determined that centrinone-B was able to change the localization patterns of de-novo methyltransferases DNMT3a and DNMT3b in mouse fibroblasts but did not change their overall protein levels. Furthermore, application of centrinone-B could affect global methylation levels in the same cells, which we speculate is due to the localization changes. Although we could not observe a direct kinase interaction between PLK4 and DNMT3a, these findings suggest that PLK4 may regulate epigenetic mechanisms by affecting the localization of these de-novo methyltransferases.
Tran, Necky, "Investigating the Functions of PLK4 in Epigenetic Regulation" (2021). Electronic Theses and Dissertations. 8540.