7-Deazaguanine modifications protect phage DNA from host restriction systems

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Geoffrey Hutinet, University of Florida, Gainesville, Florida
  • ,
  • Witold Kot
  • ,
  • Liang Cui, Campus for Research Excellence And Technological Enterprise
  • ,
  • Roman Hillebrand, Massachusetts Institute of Technology, Nitto Denko Avecia
  • ,
  • Seetharamsingh Balamkundu, Campus for Research Excellence And Technological Enterprise
  • ,
  • Shanmugavel Gnanakalai, Campus for Research Excellence And Technological Enterprise
  • ,
  • Ramesh Neelakandan, Campus for Research Excellence And Technological Enterprise
  • ,
  • Alexander B. Carstens
  • ,
  • Chuan Fa Lui, School of Biological Sciences
  • ,
  • Denise Tremblay, Université Laval
  • ,
  • Deborah Jacobs-Sera, University of Pittsburgh
  • ,
  • Mandana Sassanfar, Massachusetts Institute of Technology
  • ,
  • Yan Jiun Lee, New England Biolabs
  • ,
  • Peter Weigele, New England Biolabs
  • ,
  • Sylvain Moineau, Université Laval
  • ,
  • Graham F. Hatfull, University of Pittsburgh
  • ,
  • Peter C. Dedon, Campus for Research Excellence And Technological Enterprise, Massachusetts Institute of Technology
  • ,
  • Lars H. Hansen
  • ,
  • Valérie de Crécy-Lagard, University of Florida, Gainesville, Florida

Genome modifications are central components of the continuous arms race between viruses and their hosts. The archaeosine base (G+), which was thought to be found only in archaeal tRNAs, was recently detected in genomic DNA of Enterobacteria phage 9g and was proposed to protect phage DNA from a wide variety of restriction enzymes. In this study, we identify three additional 2'-deoxy-7-deazaguanine modifications, which are all intermediates of the same pathway, in viruses: 2'-deoxy-7-amido-7-deazaguanine (dADG), 2'-deoxy-7-cyano-7-deazaguanine (dPreQ0) and 2'-deoxy-7- aminomethyl-7-deazaguanine (dPreQ1). We identify 180 phages or archaeal viruses that encode at least one of the enzymes of this pathway with an overrepresentation (60%) of viruses potentially infecting pathogenic microbial hosts. Genetic studies with the Escherichia phage CAjan show that DpdA is essential to insert the 7-deazaguanine base in phage genomic DNA and that 2'-deoxy-7-deazaguanine modifications protect phage DNA from host restriction enzymes.

Original languageEnglish
Article number5442
JournalNature Communications
Volume10
Issue1
Number of pages12
ISSN2041-1723
DOIs
Publication statusPublished - 2019

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