Identification and Biosynthesis of Thymidine Hypermodifications in the Genomic DNA of Widespread Bacterial Viruses

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2018 Mar 21

PMID 29555775

Citations 36

Authors

Yan-Jiun Lee

Nan Dai

Shannon E Walsh

Stephanie Muller

Morgan E Fraser

Kathryn M Kauffman

Chudi Guan

Ivan R Correa Jr

Peter R Weigele

Affiliations

Soon will be listed here.

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 phage ΦW-14 and the 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 phage M6 and the phage ViI encode kinase homologs predicted to phosphorylate 5-hmdU DNA but have uncharacterized nucleotide content [Iyer et al. (2013) 41:7635-7655]. We report here the discovery and characterization of two bases, 5-(2-aminoethoxy)methyluridine (5-emdU) and 5-(2-aminoethyl)uridine (5-edU), 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-emdU in vitro. These findings point to an unexplored diversity of DNA modifications and the underlying biochemistry of their formation.

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