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Nucleic Acids Res. 2019 Jan 10;47(1):253-265. doi: 10.1093/nar/gky1125.

BREX system of Escherichia coli distinguishes self from non-self by methylation of a specific DNA site.

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Skolkovo Institute of Science and Technology, Moscow 143028, Russia.
Peter the Great St Petersburg State Polytechnic University, St Petersburg 195251, Russia.
Philip Morris International R&D, Philip Morris Products S.A., Neuchâtel 2000, Switzerland.
Institute of Biotechnology, Vilnius University, Sauletekio Avenue 7, Vilnius 10257, Lithuania.
Institute of Biochemistry, Vilnius University, Sauletekio Avenue 7, Vilnius 10257, Lithuania.
New England Biolabs, 240 County Road, Ipswich, MA 01938, USA.
Department of Biochemistry and Biophysics, Center for Phage Technology, Texas A&M University, College Station, TX 77843, USA.
Waksman Institute of Microbiology, Piscataway, NJ 08854, USA.


Prokaryotes evolved numerous systems that defend against predation by bacteriophages. In addition to well-known restriction-modification and CRISPR-Cas immunity systems, many poorly characterized systems exist. One class of such systems, named BREX, consists of a putative phosphatase, a methyltransferase and four other proteins. A Bacillus cereus BREX system provides resistance to several unrelated phages and leads to modification of specific motif in host DNA. Here, we study the action of BREX system from a natural Escherichia coli isolate. We show that while it makes cells resistant to phage λ infection, induction of λ prophage from cells carrying BREX leads to production of viruses that overcome the defense. The induced phage DNA contains a methylated adenine residue in a specific motif. The same modification is found in the genome of BREX-carrying cells. The results establish, for the first time, that immunity to BREX system defense is provided by an epigenetic modification.

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