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The article states that Uracil, a major component of RNA, is a rare constituent of DNA due to misincorporation of dUMP from dUTP or the spontaneous deamination of cytosine residues. The presence of uracil in DNA can have adverse effects. U:A pairs arising from misincorporation are not mutagenic per se since they can be corrected in the next round of replication. However, U:G mispairs arising from deamination would lead to transition mutations. Free-living organisms as well as some viruses encode uracil DNA glycosylase (UNG) and deoxyuridine 5'-triphosphate (dUTPase), which may lower the amount of uracil in DNA. By hydrolyzing dUTP, dUTPase generates dUMP for the biosynthesis of thymidine nucleotides while concurrently decreasing the availability of dUTP for misincorporation. UNG specifically recognizes uracil in DNA and initiates base excision repair by hydrolyzing the glycosylic bond linking uracil to a deoxyribose sugar. An abasic site is created that is removed by a 5'-acting apurinic/apyrimidic endonuclease and a DNase, leaving a gap filled by DNA polymerase and sealed by ligase.

Viruses that encode UNG or dUTPase include poxviruses, herpesviruses, African swine fever virus and some retroviruses. Poxviruses are large, complex viruses that reside exclusively in the cytoplasm of host cells and encode DNA polymerase and other enzymes and factors necessary to replicate their double-stranded DNA genomes. All sequenced members of the chordopoxvirus subfamily encode an UNG. Because cellular UNGs have a repair function that is unnecessary for viability, it was surprising that vaccinia virus (VACV) UNG encoded by the D4R (VACV-WR-109) open reading frame is essential for DNA replication. Subsequent mutagenesis studies, however, showed that the critical role of D4 (the protein encoded by D4R) is independent of its DNA glycosylase activity, though the latter is required for full virulence in a mouse intranasal infection model. D4 has a direct role in replication as it is complexed with other viral replication proteins and increases the processivity of the DNA polymerase. Many poxviruses, including variola virus and VACV, encode a dUTPase as well as an UNG. In contrast to UNG, however, the dUTPase encoded by the VACV F2L (VACV-WR-041) open reading frame was deleted without affecting viral replication in cell culture or virulence in a mouse infection model, although hypersensitivity to the drug (N)-methanocarbathymidine suggests that pyrimidine metabolism is altered in infected cells. African swine fever virus, distantly related to poxviruses, encodes a dUTPase that is dispensable for replication in dividing Vero cells but is required for efficient replication in non-dividing swine macrophages.

Herpesviruses are large, DNA viruses that replicate in the nucleus and encode UNG and dUTPase as well as DNA polymerase. The UNG proteins encoded by herpes simplex virus type 1 (HSV-1) and varicella zoster virus are dispensable for replication in cultured cells, but are required for efficient HSV-1 replication and latent infection in the murine nervous system. Deletion of the cytomegalovirus UNG caused a delay in viral DNA replication in quiescent human fibroblasts. It was suggested that UNG creates sites in cytomegalovirus DNA that are used for recombination-dependent replication late in ...
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