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bioRxiv · 10.1101/2024.02.29.582594

Hachiman is a genome integrity sensor

Tuck, O. T.·Adler, B. A.·Armbruster, E. G.·Lahiri, A.·Hu, J. J.·Zhou, J.·Pogliano, J.·Doudna, J. A.
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Abstract

Hachiman is a broad-spectrum antiphage defense system of unknown function. We show here that Hachiman comprises a heterodimeric nuclease-helicase complex, HamAB. HamA, previously a protein of unknown function, is the effector nuclease. HamB is the sensor helicase. HamB constrains HamA activity during surveillance of intact dsDNA. When the HamAB complex detects DNA damage, HamB helicase activity liberates HamA, unleashing nuclease activity. Hachiman activation degrades all DNA in the cell, creating phantom cells devoid of both phage and host DNA. We demonstrate Hachiman activation in the absence of phage by treatment with DNA-damaging agents, suggesting that Hachiman responds to aberrant DNA states. Phylogenetic similarities between the Hachiman helicase and eukaryotic enzymes suggest this bacterial immune system has been repurposed for diverse functions across all domains of life.

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Tuck, O. T., Adler, B. A., Armbruster, E. G., Lahiri, A., Hu, J. J., Zhou, J., Pogliano, J., Doudna, J. A.. 2024-02-29. Hachiman is a genome integrity sensor. https://doi.org/10.1101/2024.02.29.582594

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