Date of Award:
Doctor of Philosophy (PhD)
Chemistry and Biochemistry
Joan M. Hevel
Joan M. Hevel
Sean J. Johnson
Nicholas E. Dickenson
Lisa M. Berreau
Each of us begins life as a single cell containing our DNA and a complement of varied pieces of machinery capable of reading and acting on information stored in the genome. The cell copies itself and each copy makes copies. As this cycle repeats, different lineages of cells begin to take on different roles, eventually maturing into the different tissues and organs that make up a healthy organism. All of this requires exquisite coordination which requires different cells, and different parts of a cell, to be able to communicate with one another. How the mindless components of mindless cells manage to transmit and respond to information is one of the more interesting questions in biology.
While there is no single mechanism by which cells communicate, one common mechanism uses a process termed post-translational modification. In this process a protein (which is a specific type of cellular machinery) is modified, typically by the addition of a small chemical group, and this modification changes the function of the modified protein. One type of post-translational modification is called arginine methylation, in which a particular component (arginine) of certain proteins is modified by the addition of a methyl group. Arginine methylation is involved in normal cellular processes such as cellular replication and the manufacture of new proteins, and it is involved in stress responses such as DNA repair and cellular self-destruction.
Arginine methylation is conducted by a family of proteins called protein arginine methyltransferases (PRMTs). These proteins are manufactured in all eukaryotes and in all tissues. Their malfunction has been associated with several human diseases including cardiovascular disease and cancer. The processes that cause these proteins to malfunction are not well understood, nor are the basic mechanisms that drive their function. Here we describe our work toward understanding features that allow the PRMTs to recognize other proteins they need to modify, and our work characterizing a mechanism that may drive PRMT dysfunction in cancer. This work will improve our understanding of PRMT biochemistry, the roles of the PRMTs in cellular biology, and may help lead to the development of new treatments for human diseases.
Price, Owen M., "Analysis of Substrate Specificity and Dimer Disruption in Protein Arginine Methyltransferases" (2022). All Graduate Theses and Dissertations. 8654.
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