Control of nucleotide pools in mammalian cells

Abstract

The deoxyribonucleoside triphosphates (dNTPs) are produced via reduction of the corresponding nucleoside diphosphates and subsequent phosphorylation. The reduction step is catalyzed by the enzyme ribonucleoside diphosphate reductase, an enzyme which is induced in S phase cells. The activity and specificity of this enzyme is controlled by dNTPs and ATP, and this feedback mechanism provides a stringent control of the concentrations of the dNTPs themselves. The pools of the dNTPs vary during the cell cycle and are largest is S phase cells. Moreover, in S phase cells, the difference between the largest pool (dCTP) and the smallest pool (dGTP), is about 20-fold. Also, the pools are compartmentalized into cytoplasmic and nuclear pools, and this compartmentalization is most pronounced in S phase cells. In such cells, the total nuclear concentration of dNTPs is about micronM. Mainly by use of virus-infected cells, results were obtained which indicate a direct involvement of a deoxycytidine nucleotide in the regulation of DNA synthesis.