Figure 22.17 outlines the de novo and salvage synthetic pathways to thymine nucleotides. dUTP, an intermediate in the de novo pathways that begins with UDP, is readily recognized by DNA polymerases and can be incorporated into DNA in place of dTTP. The uracil from a dUMP residue in a DNA strand pairs with adenine (like thymine from a dTMP residue would), so there is no loss of or change in information in the DNA. However, dUMP residues can also arise from spontaneous deamination of dCMP. When this DNA is replicated, a mutation at the site will result because cytosine is meant to pair with guanine, not adenine.
To avoid incorporating uridines into DNA, cells have developed a rather a simple mechanism. The enzyme, dUTPase, converts dUTP (a substrate for incorporation into DNA) to dUMP (not a substrate for incorporation into DNA), and also provides a route to synthesis of thymidine nucleotides because the dUMP, in turn, is converted first to dTMP then to dTTP (Figure 22.17).
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