The vaccinia virus-encoded uracil DNA glycosylase has an essential role in viral DNA replication.
The vaccinia virus conditional-lethal temperature-sensitive (ts) mutant ts4149 is, at the nonpermissive temperature, severely impaired in its ability to replicate its DNA genome. Compared to wild type, the amount of replication is suppressed by several orders of magnitude, and the little DNA that is replicated is not converted to mature linear genomes. We have demonstrated that this "DNA-" phenotype is not the result of a failure to produce early proteins. In agreement with the DNA- phenotype, intermediate and late gene expression were not detected. Marker rescue and DNA sequencing located the mutation in ts4149 to open reading frame D4. This gene has recently been shown to encode a 25-kDa protein with uracil DNA glycosylase activity (D. T. Stuart, C. Upton, M. A. Higman, E. G. Niles, and G. McFadden (1993), J. Virol. 67, 2503-2512). We speculate on the function of this "essential" viral repair enzyme and its role(s) in viral DNA replication.
Millns
A K
AK
Department of Human Genetics, University of Manitoba, Winnipeg, Canada.
Carpenter
M S
MS
DeLange
A M
AM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D045647:DNA Glycosylases; D004261:DNA Replication / Q000235:genetics*; D004279:DNA, Viral / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D009154:Mutation; D009699:N-Glycosyl Hydrolases / Q000235:genetics*; D016366:Open Reading Frames / Q000235:genetics; D011487:Protein Conformation; D015183:Restriction Mapping; D051981:Uracil-DNA Glycosidase; D014616:Vaccinia virus / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development*; D014779:Virus Replication
D004279:DNA, Viral; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D051981:Uracil-DNA Glycosidase