Journal of General Virology

Fig. 1. Pathways for introduction of uracil residues into DNA. (A) Function of dUTPase and misincorporation of uracil into DNA. The conversion of dUTP to dUMP and PPi occurs by dUTPase activity. This conversion helps the cells to maintain a low dUTP:dTTP ratio as well as providing a substrate (dUMP) for thymidylate synthase. If the ratio is higher, the probability of misincorporation of uracil into DNA increases. Uracil-containing DNA serves as a substrate for UNG. In non-dividing cells, dUTPase levels are lower and would result in an elevated dUTP:dTTP ratio. (B) The spontaneous deamination of cytosine residues to create uracil-containing DNA leads to base excision repair. Cytosine residues can spontaneously deaminate to create uracil-containing DNA, which can be acted upon by UNG. Higher deamination rates of cytosine residues in the DNA of non-dividing cells could contribute to higher levels of uracil-containing DNA. UNG excises the uracil residue in the DNA to create an AP site. AP endonuclease cleaves the 5´ end of the AP site. The resulting single-nucleotide gap is filled in by DNA polymerase b. The remaining nick is sealed by a DNA ligase.

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