Phage-encoded factor stimulates DNA degradation by the Hna anti-phage defense system

Biochemistry, cryo-electron microscopy and single-molecule imaging show that Hna, a broadly distributed anti-phage system that triggers abortive infection, is a 3'-5' single-stranded DNA exonuclease forming an auto-inhibited dimer under physiological ATP. A phage-encoded single-stranded DNA-binding protein (5A SSB) destabilizes the dimer and drives dysregulated nuclease activation, while phage escape mutants encode SSB variants that evade Hna.