DNA glycosylases provide antiviral defence in prokaryotes.

Autor: Hossain AA; Laboratory of Bacteriology, The Rockefeller University, New York, NY, USA., Pigli YZ; Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA., Baca CF; Laboratory of Bacteriology, The Rockefeller University, New York, NY, USA., Heissel S; Proteomics Resource Center, The Rockefeller University, New York, NY, USA., Thomas A; Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA., Libis VK; Laboratory of Genetically Encoded Small Molecules, The Rockefeller University, New York, NY, USA., Burian J; Laboratory of Genetically Encoded Small Molecules, The Rockefeller University, New York, NY, USA., Chappie JS; Department of Molecular Medicine, Cornell University, Ithaca, NY, USA., Brady SF; Laboratory of Genetically Encoded Small Molecules, The Rockefeller University, New York, NY, USA., Rice PA; Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA. price@uchicago.edu., Marraffini LA; Laboratory of Bacteriology, The Rockefeller University, New York, NY, USA. marraffini@rockefeller.edu.; Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA. marraffini@rockefeller.edu.
Jazyk: angličtina
Zdroj: Nature [Nature] 2024 May; Vol. 629 (8011), pp. 410-416. Date of Electronic Publication: 2024 Apr 17.
DOI: 10.1038/s41586-024-07329-9
Abstrakt: Bacteria have adapted to phage predation by evolving a vast assortment of defence systems 1 . Although anti-phage immunity genes can be identified using bioinformatic tools, the discovery of novel systems is restricted to the available prokaryotic sequence data 2 . Here, to overcome this limitation, we infected Escherichia coli carrying a soil metagenomic DNA library 3 with the lytic coliphage T4 to isolate clones carrying protective genes. Following this approach, we identified Brig1, a DNA glycosylase that excises α-glucosyl-hydroxymethylcytosine nucleobases from the bacteriophage T4 genome to generate abasic sites and inhibit viral replication. Brig1 homologues that provide immunity against T-even phages are present in multiple phage defence loci across distinct clades of bacteria. Our study highlights the benefits of screening unsequenced DNA and reveals prokaryotic DNA glycosylases as important players in the bacteria-phage arms race.
(© 2024. The Author(s).)
Databáze: MEDLINE