Bacteriophage PBS2-induced inhibition of uracil-containing DNA degradation

Katz, Gerson; Price, Alan R.; Pomerantz, M J

doi:10.1128/jvi.20.2.535-538.1976

Cited by 30 publications

(21 citation statements)

References 17 publications

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“…Thus, the relative plaque-forming efficiencies, the kinetics of one-step growth, the burst sizes, and, the lengths of the progeny single-stranded DNAs were the same in these two hosts. These results can be explained in terms of the findings of several workers (2,4,6,18) that phage PBS1 produces an inhibitor of the host Nglycosidase shortly after infection. In our own experiments, the N-glycosidase activity of the 168T host cells decreased more than 50% within 5 min and diminished completely within 10 min after infection.…”

Section: Resultssupporting

confidence: 52%

Isolation and Characterization of a Bacillus subtilis Mutant with a Defective N -Glycosidase Activity for Uracil-Containing Deoxyribonucleic Acid

Makino¹,

Munakata²

1977

J Bacteriol

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Crude cell extracts ofBacillus subtilis 168T exhibit enzyme activity capable of releasing free uracil from phage PBS1 deoxyribonucleic acid (DNA) in the presence of ethylenediaminetetraacetate. By measuring the enzyme activity in 300 clones that emanated from mutagenized cells, we obtained a mutant strain that did not show this N-glycosidase activity. The mutant strain, designated as TKJ6901 (urg-1) exhibited no physiological abnormalities. We observed the intracellular action of the enzyme by following the fate of uracil-containing DNA in cells from wild-type and mutant cultures. When infection with phage PBS1 was allowed in the presence of chloramphenicol, extensive degradation of phage DNA was observed only in the wild-type cells. When bromouracil residues were converted to uracil residues by ultraviolet light irradiation in the presence of cysteamine, the DNA was extensively fragmented in the wild-type cells. These single-strand breaks were rejoined upon postirradiation incubation. In contrast, such fragmentation of the DNA was not observed in the mutant cells, indicating that the uracil residues were not removed from the DNA. This demonstrated that the N-glycosidase activity was involved in the excision of uracil in DNA. A transfornation assay with four types of recipient strains with combinations ofN-glycosidase and DNA polymerase I deficiencies indicated that DNA polymerase I was involved in the later steps of this base excision repair pathway initiated by the action of the N-glycosidase. Recently, several authors described a new class of deoxyribonucleic acid (DNA)-degrading enzymes that liberate unusual bases from DNA by catalyzing the hydrolysis of the N-glycosidic bond between a base and a deoxyribose sugar. Such an N-glycosidase specific for uracil residues in DNA has been observed in extracts of Escherichia coli (8), Bacillus subtilis (2, 4, 6), and human (15) cells. Another type ofN-glycosidase activity specific for 3-methyladenine and/ or 06-methylguanine residues produced in

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Section: Resultssupporting

confidence: 52%

Isolation and Characterization of a Bacillus subtilis Mutant with a Defective N -Glycosidase Activity for Uracil-Containing Deoxyribonucleic Acid

Makino¹,

Munakata²

1977

J Bacteriol

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“…Recent in vitro studies have shown that the Mu mom' DNA is at least partially resistant to the action of several type II restriction endonucleases, whereas Mu mom-DNA is sensitive. By comparing and aligning the recognition sequences of restriction enzymes whose cleavage is affected by the Mom function, we deduced a consensus recognition sequence for Mom of 5'-C/G-A-G/C-N-Py-3' (63). By checking the recognition sequences of E. coli restriction enzymes (Table 1), one can see that the sequences for EcoPl, EcoP15, EcoB, and EcoK all overlap with the Mom recognition sequence, but that the EcoRI sequence differs completely, so that the in vivo protection against the first group of restriction endonucleases, but not against EcoRI, is understandable.…”

Section: Mumentioning

confidence: 99%

“…This potentially mutagenic lesion is normally removed by an enzyme called uracil-N-glycosylase, which cleaves the N-glycosidic bond (81). Phages like PBS2, whose DNA normally contains uracil instead of thymine, direct the synthesis of a protein that inhibits the host uracil Nglycosylase (35,62,63,123). The evolution of such an inhibitor demonstrates the importance of the unusual base uracil for the phage.…”

Section: Unusual Bases In Phage Dnamentioning

confidence: 99%

Bacteriophage survival: multiple mechanisms for avoiding the deoxyribonucleic acid restriction systems of their hosts.

Krüger¹,

Bickle²

1983

Microbiological Reviews

179

101

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“…Cellular utilisation of Ung activity is not limited to its role in DNA repair (Figure 4), thus Ung is observed to play important roles in other key cellular programs, such as innate cellular immunity as a frontline defence against viral pathogens. The importance of this role for Ung is underlined by the fact that diverse virus lineages, whether targeting prokaryotes or eukaryotes, actively silence Ung at the mRNA or/and at the protein level [41,[53][54][55][56][57][58][59][60]. It would appear that viruses, in general, are sensitive to uracil in DNA for varying reasons.…”

Section: The Ung-type Uracil-dna Glycosylase Is Central To the Host Pmentioning

confidence: 99%

The Essential Co-Option of Uracil-DNA Glycosylases by Herpesviruses Invites Novel Antiviral Design

Savva

2020

Microorganisms

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Vast evolutionary distances separate the known herpesviruses, adapted to colonise specialised cells in predominantly vertebrate hosts. Nevertheless, the distinct herpesvirus families share recognisably related genomic attributes. The taxonomic Family Herpesviridae includes many important human and animal pathogens. Successful antiviral drugs targeting Herpesviridae are available, but the need for reduced toxicity and improved efficacy in critical healthcare interventions invites novel solutions: immunocompromised patients presenting particular challenges. A conserved enzyme required for viral fitness is Ung, a uracil-DNA glycosylase, which is encoded ubiquitously in Herpesviridae genomes and also host cells. Research investigating Ung in Herpesviridae dynamics has uncovered an unexpected combination of viral co-option of host Ung, along with remarkable Subfamily-specific exaptation of the virus-encoded Ung. These enzymes apparently play essential roles, both in the maintenance of viral latency and during initiation of lytic replication. The ubiquitously conserved Ung active site has previously been explored as a therapeutic target. However, exquisite selectivity and better drug-like characteristics might instead be obtained via targeting structural variations within another motif of catalytic importance in Ung. The motif structure is unique within each Subfamily and essential for viral survival. This unique signature in highly conserved Ung constitutes an attractive exploratory target for the development of novel beneficial therapeutics.

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Bacteriophage PBS2-induced inhibition of uracil-containing DNA degradation

Cited by 30 publications

References 17 publications

Isolation and Characterization of a Bacillus subtilis Mutant with a Defective N -Glycosidase Activity for Uracil-Containing Deoxyribonucleic Acid

Isolation and Characterization of a Bacillus subtilis Mutant with a Defective N -Glycosidase Activity for Uracil-Containing Deoxyribonucleic Acid

Bacteriophage survival: multiple mechanisms for avoiding the deoxyribonucleic acid restriction systems of their hosts.

The Essential Co-Option of Uracil-DNA Glycosylases by Herpesviruses Invites Novel Antiviral Design

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