dNTPs and maintenance of genome stability

The four dNTPs (dATP, dTTP, dCTP, and dGTP) are the building blocks of DNA. A balanced supply and a correct overall concentration of dNTPs are key prerequisites for faithful genome replication. These requirements, along with the fact that the concentrations of dNTPs fluctuate during the cell cycle, mean that the production of dNTPs must be tightly regulated through multiple mechanisms.   By introducing point mutations in the genes responsible for the production of dNTPs, I have created different budding yeast and mouse models that have altered dNTP metabolism. Using these models, I am investigating how imbalanced dNTP pools alter the fidelity of DNA replication and how different replication errors are recognized and repaired. I will discuss how metabolic changes in the dNTP pool balance affect nuclear and mitochondrial DNA stability, the development of cancer, and other genetic disorders.