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Deoxyribonucleotide Precursor Synthesis

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The precursors of DNA synthesis are the four deoxyribonucleoside triphosphates, dATP, dGTP, dCTP, and dTTP. The triphosphates are synthesized from the corresponding ribose nucleoside diphosphates by the pathway shown in Figure 1.5. In the first step, the enzyme ribonucleotide reductase reduces (i.e., removes an oxygen from) the ribose sugar to produce the deoxyribose sugar by changing the hydroxyl group at the 2' position (the second carbon) of the sugar to a hydrogen. Then, an enzyme known as a kinase adds a phosphate to the deoxynucleoside diphosphate to make the deoxynucleoside triphosphate precursor.

The deoxynucleoside triphosphate dTTP is synthesized by a somewhat different pathway from the other three. The first step is the same. Ribonucleotide reductase synthesizes the nucleotide dUDP (deoxyuridine diphosphate) from the ribose UDP. However, from then on, the pathway differs. A phosphate is added to make dUTP, and the dUTP is converted to dUMP by a phosphatase that removes two of the phosphates. This molecule is then converted to dTMP by the enzyme thymidylate synthetase, using tetrahydrofolate to donate a methyl group. Kinases then add two phosphates to the dTMP to make the precursor dTTP.

Snyder and Champness Molecular Genetics of Bacteria

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