College of Science
129 Investigating DNA Proteins MutT and MutY in the A:T to C:G Transversion MutationStudent’s
Bridget Raymundo
Faculty Mentor: Martin Horvath (School of Biological Science, University of Utah)
Genetic mutations heavily impact advances in genetic research. There is a need for an efficient method of A:T to C:G mutations. My project examines and demonstrates the instrumental role of MutT and MutY in these mutations as further insight is shined on the functions of both. My hypothesis is that inhibition of MutT and the incorporation of functional MutY will increase mutation frequencies.
The experiment begins with my search for effective MutT inhibitors, docking the expected ligand-protein reaction, and building a literary basis for my research. To compare mutation frequencies, I have conducted multiple preliminary mutation assays and organized my results into a boxplot. The results of my mutation assays led me to conclude I needed to confirm the identity and characteristics of my strains by DNA sequencing. Currently, I am able to compare the DNA sequences of selected mutated and non-mutated E. coli strains to identify the presence or absence of MutY. As the next course of action, all my work up to now would be repeated with the addition of MutT inhibitors to lead into the main investigation of the role of MutT in the DNA replication process.
Bibliography
Demir, Merve, L Peyton Russelburg, Wen-Jen Lin, Carlos H Trasviña-Arenas, Beili Huang, Philip K Yuen, Martin P Horvath, and Sheila S David. 2023. “Structural Snapshots of Base Excision by the Cancer-Associated Variant MutY N146S Reveal a Retaining Mechanism.” Nucleic Acids Research, January, gkac1246. https://doi.org/10.1093/nar/gkac1246.
Gad, Helge, Tobias Koolmeister, Ann-Sofie Jemth, Saeed Eshtad, Sylvain A. Jacques, Cecilia E. Ström, Linda M. Svensson, et al. 2014. “MTH1 Inhibition Eradicates Cancer by Preventing Sanitation of the DNTP Pool.” Nature 508 (7495): 215–21. https://doi.org/10.1038/nature13181.
Russelburg, L. Peyton, Valerie L. O’Shea Murray, Merve Demir, Kyle R. Knutsen, Sonia L. Sehgal, Sheng Cao, Sheila S. David, and Martin P. Horvath. 2020. “Structural Basis for Finding OG Lesions and Avoiding Undamaged G by the DNA Glycosylase MutY.” ACS Chemical Biology 15 (1): 93–102. https://doi.org/10.1021/acschembio.9b00639.
Woods, Ryan D., Valerie L. O’Shea, Aurea Chu, Sheng Cao, Jody L. Richards, Martin P. Horvath, and Sheila S. David. 2016. “Structure and Stereochemistry of the Base Excision
Repair Glycosylase MutY Reveal a Mechanism Similar to Retaining Glycosidases.” Nucleic Acids Research 44 (2): 801–10. https://doi.org/10.1093/nar/gkv1469.
Yin, Yizhen, and Fener Chen. 2020. “Targeting Human MutT Homolog 1 (MTH1) for Cancer Eradication: Current Progress and Perspectives.” Acta Pharmaceutica Sinica B 10 (12): 2259–71. https://doi.org/10.1016/j.apsb.2020.02.012.
