Date of Graduation

Spring 2015

Degree

Master of Science in Cell and Molecular Biology

Department

Biomedical Sciences

Committee Chair

Joshua Smith

Abstract

Histone deacetylases (HDACs) are proteins that remove acetyl groups from histone tails, leading to tightly compacted heterochromatin. Recently, a type of NAD+-dependent deacetylases known as sirtuins has been found to be associated with an extensive number of roles within the cell. In humans, there are seven known sirtuins (SIRT1-7). Sirt2 localizes to the nucleus and cytoplasm and is involved in several functions including cell-cycle control, while Sirt3 localizes in the mitochondria and plays a role in the regulation of mitochondrial proteins like IDH2 and MnSOD and reactive oxygen species (ROS). Both of these sirtuins have been linked to aging and cancer. In Tetrahymena thermophila, several homologs of the SIRT2 and SIRT3 genes exist including THD13, THD14, THD15, and THD16 as identified through bioinformatics. The aim of this project is to further elucidate the contribution of Thd13, Thd15, and Thd16 in DNA repair mechanisms, particularly their involvement in the onset of cancer and age related disease. Expression of the THD13 gene displayed a substantial change following exposure to methyl methanesulfonate (MMS), and fluorescent imaging confirmed possible mitochondrial localization. Bioinformatics and literature review illustrate the extensive roles of Sirt2 and Sirt3 in repair, genome stability, and disease; further research on these T. thermophila homologs may elucidate the roles these enzymes have in cellular genome stability and longevity.

Keywords

histone deacetylase, sirtuin, Sirt2, Sirt3, DNA damage, genome stability, cancer, aging, Tetrahymena thermophila

Subject Categories

Medical Molecular Biology

Copyright

© Micheala Alexis Jordan Steinmetz

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