Identification and biosynthesis of thymidine hypermodifications in the genomic DNA of widespread bacterial viruses.

Autor: Yan-Jiun Lee, Nan Dai, Walsh, Shannon E., Müller, Stephanie, Fraser, Morgan E., Kauffman, Kathryn M., Guan, Chudi, Corrêa Jr., Ivan R., Weigele, Peter R.
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Zdroj: Proceedings of the National Academy of Sciences of the United States of America; 4/3/2018, Vol. 115 Issue 14, pE3116-E3125, 10p
Abstrakt: 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 FW-14 and the Bacillus phage SP10 contain the hypermodified pyrimidines α-putrescinylthymidine and α-glutamylthymidine, respectively. These bases derive fromthe modification of 5-hydroxymethyl-2'-deoxyuridine (5-hmdU) in newly replicated phage DNA via a pyrophosphorylated intermediate. Like FW-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 41:7635-7655]. 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index