A uracil-DNA glycosylase inhibitor encoded by a non-uracil containing viral DNA.
Uracil-DNA glycosylase (UDG) is an enzyme involved in the base excision repair pathway. It specifically removes uracil from both single-stranded and double-stranded DNA. The genome of the Bacillus subtilis phage 29 is a linear double-stranded DNA with a terminal protein covalently linked at each 5'-end. Replication of 29 DNA starts by a protein-priming mechanism and generates intermediates that have long stretches of single-stranded DNA. By using in vivo chemical cross-linking and affinity chromatography techniques, we found that UDG is a cellular target for the early viral protein p56. Addition of purified protein p56 to B. subtilis extracts inhibited the endogenous UDG activity. Moreover, extracts from 29-infected cells were deficient in UDG activity. We suggested that inhibition of the cellular UDG is a defense mechanism developed by 29 to prevent the action of the base excision repair pathway if uracil residues arise in their replicative intermediates. Protein p56 is the first example of a UDG inhibitor encoded by a non-uracil-containing viral DNA.
Serrano-Heras
Gemma
G
Instituto de Biología Molecular "Eladio Viñuela" (Consejo Superior de Investigaciones Científicas), Universidad Autónoma, Cantoblanco, 28049 Madrid, Spain.
Salas
Margarita
M
Bravo
Alicia
A
D017103:Bacillus Phages / Q000378:metabolism*; D001412:Bacillus subtilis / Q000201:enzymology / Q000378:metabolism; D002846:Chromatography, Affinity; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004247:DNA; D045647:DNA Glycosylases / Q000737:chemistry; D004260:DNA Repair; D004279:DNA, Viral / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016678:Genome; D016680:Genome, Bacterial; D008957:Models, Genetic; D009699:N-Glycosyl Hydrolases / Q000737:chemistry; D011485:Protein Binding; D013379:Substrate Specificity; D014498:Uracil / Q000737:chemistry; D051981:Uracil-DNA Glycosidase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D014764:Viral Proteins / Q000737:chemistry
D003432:Cross-Linking Reagents; D004279:DNA, Viral; D004791:Enzyme Inhibitors; D014764:Viral Proteins; D014498:Uracil; D004247:DNA; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D051981:Uracil-DNA Glycosidase