Young Woo Kim | 2025 I.S. Symposium

Name: Young Woo Kim
Title: Interplay between Ribonucleotide Reductase, Peroxiredoxins and Disulfide Reduction Pathways in Regulating Genomic Instability in Baker’s Yeast
Major: Biochemistry and Molecular Biology
Minor: Music
Advisors: James West; Paul Edmiston

Genetic factors influencing genomic instability, a hallmark of cancer, have been identified as protecting agents against oxidative stress and controlling agents of the rate of dNTP synthesis in Saccharomyces cerevisiae. Disulfide reductases, such as thioredoxins (Trx) and glutaredoxins (Grx), connect oxidant defense enzymes, such as thiol-specific antioxidants (Tsa), and dNTP biosynthesis pathways, but the interplay between these processes in regulating genomic stability remains unclear. In this study, the complex interactions between Rnr, an enzyme that catalyzes the rate-limiting step in dNTP biosynthesis, oxidant defense enzymes like Tsa1 and Tsa2, disulfide reduction enzymes like Grx1 and Trx1, and their respective reductases Glr1 and Trr1 are investigated to examine their collective influence on maintaining genomic instability in baker’s yeast. Initially, an ordinary differential equation (ODE) model was made with apparent rates to examine if alterations to the interplay cause an imbalance in dNTPs. The removal of oxidant defense enzymes and disulfide reduction pathways led to an imbalance in dNTP levels, caused by allosteric activation and inhibition from dNTPs produced. To examine the validity of the model, mutation rates of S. cerevisiae lacking the core oxidant defense enzymes, Tsa1 and Tsa2, and Glr1, a glutathione reductase involved in maintaining a cell’s redox state, were measured to examine their influence on genomic stability. Aligning with previous work, tsa1Δtsa2Δ strain showed an increase in mutation rate. However, tsa1Δtsa2Δglr1Δ variant had a lower mutation rate, suggesting that there is a genetic interaction between Tsa1, Tsa2 and Glr1 in maintaining genomic instability. Further study can be done to examine if the hyperactivity of Rnr caused by excessive allocation of disulfide reductases results in genomic instability.

Posted in Symposium 2025 on May 1, 2025.