7-Deazaguanine modifications protect phage DNA from host restriction systems

Geoffrey Hutinet (), Witold Kot, Liang Cui, Roman Hillebrand, Seetharamsingh Balamkundu, Shanmugavel Gnanakalai, Ramesh Neelakandan, Alexander B. Carstens, Chuan Fa Lui, Denise Tremblay, Deborah Jacobs-Sera, Mandana Sassanfar, Yan-Jiun Lee, Peter Weigele, Sylvain Moineau, Graham F. Hatfull, Peter C. Dedon, Lars H. Hansen and Valérie Crécy-Lagard ()
Additional contact information
Geoffrey Hutinet: University of Florida
Witold Kot: Aarhus University
Liang Cui: Campus for Research Excellence and Technological Enterprise
Roman Hillebrand: Massachusetts Institute of Technology
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
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
Lars H. Hansen: Aarhus University
Valérie Crécy-Lagard: University of Florida

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-13384-y

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