Identification and biosynthesis of thymidine hypermodifications in the genomic DNA of widespread bacterial viruses.
Proc Natl Acad Sci U S A
; 115(14): E3116-E3125, 2018 04 03.
Article
em En
| MEDLINE
| ID: mdl-29555775
ABSTRACT
Certain viruses of bacteria (bacteriophages) enzymatically hypermodify their DNA to protect their genetic material from host restriction endonuclease-mediated cleavage. Historically, it has been known that virion DNAs from the Delftia phage ΦW-14 and the Bacillus phage SP10 contain the hypermodified pyrimidines α-putrescinylthymidine and α-glutamylthymidine, respectively. These bases derive from the modification of 5-hydroxymethyl-2'-deoxyuridine (5-hmdU) in newly replicated phage DNA via a pyrophosphorylated intermediate. Like ΦW-14 and SP10, the Pseudomonas phage M6 and the Salmonella phage ViI encode kinase homologs predicted to phosphorylate 5-hmdU DNA but have uncharacterized nucleotide content [Iyer et al. (2013) Nucleic Acids Res 417635-7655]. We report here the discovery and characterization of two bases, 5-(2-aminoethoxy)methyluridine (5-NeOmdU) and 5-(2-aminoethyl)uridine (5-NedU), in the virion DNA of ViI and M6 phages, respectively. Furthermore, we show that recombinant expression of five gene products encoded by phage ViI is sufficient to reconstitute the formation of 5-NeOmdU in vitro. These findings point to an unexplored diversity of DNA modifications and the underlying biochemistry of their formation.
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Base de dados:
MEDLINE
Assunto principal:
Timidina
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Bactérias
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Infecções Bacterianas
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Proteínas de Bactérias
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Bacteriófagos
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Uridina
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DNA Viral
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article