Characterization of Tetrahymena Histone Deacetylase 13 and 15, Sirt3 Homologs That Change Expression in Response to Genotoxic Stressors

Chromatin is tightly compacted DNA wrapped around a histone tetramer core. The accessibility of the DNA is regulated by either the addition or subtraction of chemical groups to the lysine tails of the histone proteins. These modifications, such as phosphorylation or methylation, can lead to a conformational change and access to genes. The histone deacetylases (HDACs) are one such chromatin-altering class that removes acetyl groups from histones. This removal leads to a gene silencing effect. Sirtuins comprise an entire class of HDACs that are specifically NAD+-dependent. Research has shown that sirtuins affect a variety of cellular responses and hold promise as therapeutic agents for a number of diseases. Seven sirtuins (SIRT1-SIRT7) have been identified in human, and eleven homologs have been found in Tetrahymena (THD8-THD18). These proteins have been shown to play either a direct or a support role during repair in the presence of DNA damage. The goal of this project was focused on eludicating possible roles for Tetrahymena sirtuins during DNA damage. Expression profiles were performed for Thd13 and Thd15 to investigate their roles in DNA damage repair. Findings showed upregulation of the genes mostly for MMS and H2O2 at various points after exposure, suggesting a possible role of double-strand break repair and oxidative damage response