A bacteriophage-encoded protein gp119 suppresses deoxyinosine repair to protect hypermutated viral genome
Chensi Miao, Weikuan Liu, Xuyang Ren, Yanmin Zhang, Xing Chang
Journal：iScience
IF：4.1
DOI：10.1016/j.isci.2026.115532
PMID：
Published：2026-03-30
research field：分子生物学基因工程合成生物学DNA修复病毒学
Abstract
Bacteriophage Fletcherviruses completely replace deoxyguanosine (dG) with deoxyinosine (dI) in their genomes. Through a genetic screen of 172 open reading frames from Fletchervirus NCTC 12673, we identified gp119, an ArdA-like protein that inhibits dI repair and enhances the efficiency of A-to-G conversions mediated by adenine base editors (ABEs) in Escherichia coli . Structural modeling suggests that gp119 functions as a multifunctional DNA mimic protein that specifically targets endonuclease V (EndoV), a key enzyme in dI repair. In vitro enzymatic assays confirm that gp119 potently suppresses EndoV-mediated cleavage of dI-containing DNA oligonucleotide. Our study demonstrates that systematic exploration of phage genomes can uncover molecular mechanisms with both fundamental and biotechnological significance.
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