Mechanisms of dNTP supply that play an essential role in maintaining genome integrity in eukaryotic cells

Optimization of intracellular concentrations of dNTPs is critical for the fidelity of DNA synthesis during DNA replication and repair because levels that are too high or too low can easily lead to increased rates of mutagenesis. Recent advances in the analysis of intracellular concentrations of dNTPs have suggested that eukaryotes use diverse mechanisms in supplying dNTPs for DNA synthesis during DNA replication and repair. The enzyme ribonucleotide reductase (RNR) is a key enzyme involved in the synthesis of dNTPs. We found that Tip60-dependent recruitment of RNR at sites of DNA damage is essential for supplying a sufficient amount of dNTPs for mammalian DNA repair. In this review, we focus on recent findings related to RNR regulation in eukaryotes of the dNTPs supplied for DNA synthesis. We also discuss the effect of this regulation on mutagenesis and tumorigenesis. (Cancer Sci 2010; 101: 2505-2509).