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7-Deazaguanine modifications protect phage DNA from host restriction systems

Author

Listed:
  • Geoffrey Hutinet

    (University of Florida)

  • Witold Kot

    (Aarhus University)

  • 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

    (Aarhus University)

  • Chuan Fa Lui

    (Nanyang Technological University)

  • Denise Tremblay

    (Université Laval
    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
    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

    (Aarhus University)

  • Valérie Crécy-Lagard

    (University of Florida
    University of Florida, Genetics Institute)

Abstract

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.

Suggested Citation

  • Geoffrey Hutinet & Witold Kot & Liang Cui & Roman Hillebrand & Seetharamsingh Balamkundu & Shanmugavel Gnanakalai & Ramesh Neelakandan & Alexander B. Carstens & Chuan Fa Lui & Denise Tremblay & Debora, 2019. "7-Deazaguanine modifications protect phage DNA from host restriction systems," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13384-y
    DOI: 10.1038/s41467-019-13384-y
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