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Regulation of DNA precursors in mammalian cells during proliferation and quiescence: implications for the stability of the nuclear and mitochondrial genomes in health and disease. Disturbances of the relative concentrations and the dynamics of DNA precursor (dNTP) pools affect the accuracy and efficiency of DNA synthesis. Main effects are increased frequency of mutations, structural alterations of chromosomes, destabilization or depletion of the mitochondrial genome. We study the mechanisms that keep dNTP pools in tune with the needs of nuclear and mitochondrial DNA replication and repair. The enzyme network includes both synthetic and catabolic enzymes and we analyze their functional interactions in cultured mammalian cells.

Relationships between telomere metabolism and dNTP pool sizes. The aim of the project is to examine the effect of dNTP imbalance on telomere length by quantitative fluorescence in situ hybridization (Q-FISH) and quantitative PCR. Deoxynucleotide imbalance and mtDNA stability in mammalian cells. The aim of the project is to understand cellular mechanisms for the maintenance of mtDNA integrity and copy number by Next Generation Sequencing and quantitative PCR.