Gabija restricts phages that antagonize a conserved host DNA repair complex

Area of Science:

• Bacteriophage biology
• Molecular mechanisms of immunity
• DNA repair and defense systems

Background:

• Bacteriophage defense systems like restriction-modification and CRISPR-Cas use DNA specificity to identify invaders.
• The mechanism of self vs. non-self discrimination by the Gabija nuclease-helicase anti-phage system is currently unknown.

Purpose of the Study:

• To elucidate the mechanism by which the Gabija anti-phage system discriminates between self and foreign DNA.
• To understand how phages are sensitized to Gabija and how Gabija targets invaders.

Main Methods:

• Investigated the interaction between Gabija, phage DNA, and host repair proteins (RecBCD).
• Analyzed the role of phage-encoded DNA end-binding proteins (Gam_Mu) in sensitizing phages to Gabija.
• Examined the impact of RecBCD activity on Gabija targeting of self and foreign DNA.

Main Results:

• Phage-encoded DNA end-binding proteins that antagonize host RecBCD sensitize phages to Gabija.
• Gabija prevents phage genome circularization early in infection by targeting linear DNA lacking RecBCD.
• Phage and plasmid DNA sensitivity to Gabija is mediated by a phage exonuclease and ssDNA-annealing protein.

Conclusions:

• Gabija identifies foreign invaders by antagonizing the circularization of linear DNA that lacks RecBCD.
• RecBCD activity is crucial for protecting self-DNA from Gabija and for sensitizing escape phages.
• This provides a novel mechanism for anti-phage defense based on DNA end recognition and host repair antagonism.