Uracil-DNA N-Glycosylase

dUTP is an intermediate in the synthesis of dTTP. dUTP can also be readily incorporated into DNA by DNA polymerases in place of dTTP, because uracil can base-pair with adenine. When this occurs, there is no loss of or change in information. Another source of uracil in DNA is the spontaneous deamination of cytosine residues, which results in formation of a G-U base pair. When this occurs, there is a change in information, because subsequent replications of the U-containing strand would give rise to an A-T base pair, instead. As a result, cells employ two systems to prevent accumulation of deoxyuridylate residues in DNA.

First, cells contain an enzyme, dUTPase, which cleaves dUTP to dUMP + PPi.

Second, the enzyme uracil-DNA N-glycosylase removes any dUMP residues that make it into DNA. Figure 24.35 shows how this repair system works. As seen in the figure, the uracil base is clipped from the sugar, followed by an adjacent nick in the DNA strand which contained the uracil. Nick translation by DNA polymerase I removes the apyrimidinic moiety and replaces it with dTMP. Finally, DNA ligase (see here) reseals the nick.

See also: Biosynthesis of Thymine Deoxyribonucleotides (from Chapter 22), Deoxyuridine Nucleotide Metabolism (from Chapter 22), Replication Complexes