Exploring the Impact of HDAC Inhibitors on UV-Induced DNA Damage Repair in Tetrahymena thermophila.
Discipline: Biological Sciences
Subcategory: cell & molecular biology
Session: 3
Room: 1 - Hanover DE
Talon Justice Prince Asiedu Mitchell - Missouri State University
The stability of a cell’s genetic information is essential for preventing diseases and maintaining cellular health, relying on efficient DNA repair mechanisms. In eukaryotic cells, DNA is compacted into chromatin, with tightly packed heterochromatin restricting access to repair machinery and more relaxed euchromatin facilitating repair. Histone acetylation generally opens chromatin, promoting DNA repair, while deacetylation tightens it. This study aims to test the hypothesis that inhibiting histone deacetylases (HDACs) before or after UV exposure impacts the DNA repair response in Tetrahymena thermophila. This research is significant because understanding how chromatin dynamics affect DNA repair could inform cancer treatment strategies, where enhancing or suppressing DNA repair is critical. Nicotinamide, an HDAC inhibitor and a common sunscreen ingredient, is of particular interest due to its role in protecting against UV-induced DNA damage and its implications for skin cancer prevention. In this study, Tetrahymena thermophila, a model organism with two nuclei that exhibit distinct chromatin compaction states, was used to explore the impact of HDAC inhibition. Cells were treated with 25 mM Nicotinamide, which targets Class III HDACs. Non-lethal doses were determined through dose-response experiments previously done. The study included both a pre-treatment and post-treatment group for HDAC inhibition, with cells exposed to 100 J/m2 of UV light, a dosage known to induce DNA damage. Controls consisted of untreated cells and cells exposed to UV without HDAC inhibitor treatment. Cell viability was measured to assess the impact of HDAC inhibition on DNA repair. Preliminary results indicate that pre-treatment with HDAC inhibitors leads to higher survival rates compared to post-treatment. This suggests that inhibiting HDACs before UV exposure may enhance chromatin accessibility, facilitating more effective DNA repair. In contrast, post-treatment inhibition showed reduced cell viability, possibly due to sustained chromatin relaxation that may disrupt subsequent repair processes. These findings highlight the importance of timing in HDAC inhibition and its impact on chromatin dynamics. In conclusion, the study suggests that HDAC inhibitors can modulate the DNA repair process, with implications for improving the effectiveness of cancer therapies that rely on DNA-damaging agents. Future research will focus on identifying specific HDACs involved in the repair process and exploring how HDAC inhibition interacts with other DNA repair pathways. Additionally, understanding how these processes vary between different chromatin states in Tetrahymena could provide deeper insights into chromatin regulation during DNA damage response.
Funder Acknowledgement(s): I would like to acknowledge the support and guidance I received throughout this research project. My gratitude goes to the Smith Lab, led by Dr. Joshua Smith, who funded my research and provided invaluable mentorship. I am especially thankful to Emma Liimatta, a member of the Smith Lab, for her assistance with my initial experiments and for helping me become comfortable with research techniques. I also appreciate the support of the Louis Stokes Alliances for Minority Participation (LSAMP) at Missouri State University. Special thanks to my LSAMP advisor, Dr. Danniel Moreno; Dr. Tayo Obafemi-Ajayi, who oversees the Missouri State LSAMP chapter; and Karina Gbadagri, the LSAMP graduate assistant, for their encouragement and guidance.
Faculty Advisor: Dr. Joshua Smith, Missouri State University, Dr. Daniel Moreno, Missouri State University, Dr. Tayo Obafemi-Ajayi, Missouri State University, tayoobafemiajayi@missouristate.edu
Role: For this research, I conducted experiments on the role of histone deacetylases (HDACs) in DNA repair using Tetrahymena thermophila as a model organism. I worked with HDAC inhibitors, specifically Nicotinamide, to evaluate their impact on UV-induced DNA damage. I compared cell survival rates with pre- and post-treatment of HDAC inhibitors. My experiments aimed to explore how the timing of HDAC inhibition affects DNA repair, contributing to potential cancer treatment insights.