Abstract
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.
Highlights
Uracil in DNA may arise from spontaneous deamination of cytosine and from the occasional use of dUTP instead of dTTP during DNA replication
We suggested that inhibition of the cellular uracil-DNA glycosylase (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
We propose that inhibition of the host UDG by protein p56 ensures the integrity of the 29 replicative intermediates if uracil residues arise either by cytosine deamination or dUMP misincorporation
Summary
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. Unlike phage PBS2, the genome of the B. subtilis phage 29 does not contain uracil residues It is a linear double-stranded DNA, with a terminal protein (TP) covalently linked at both 5Ј-ends. We propose that inhibition of the host UDG by protein p56 ensures the integrity of the 29 replicative intermediates if uracil residues arise either by cytosine deamination or dUMP misincorporation.
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