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.
We are investigating (i) how the genome integrity checkpoint regulates the concentration of dNTPs and how dNTPs regulate the activation of the genome integrity checkpoint, and (ii) how imbalanced dNTP pools affect the fidelity of replication and genome stability and how different replication errors are recognized and repaired. We hope to understand how metabolic changes in the dNTP pool balance affect aging, the development of cancer, and other genetic disorders.