Tuck Owen T, Adler Benjamin A, Armbruster Emily G, Lahiri Arushi, Hu Jason J, Zhou Julia, Pogliano Joe, Doudna Jennifer A
Department of Chemistry, University of California, Berkeley, Berkeley, CA USA.
Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA USA.
bioRxiv. 2024 Feb 29:2024.02.29.582594. doi: 10.1101/2024.02.29.582594.
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.
八幡是一种功能未知的广谱抗噬菌体防御系统。我们在此表明，八幡由异源二聚体核酸酶-解旋酶复合物HamAB组成。HamA以前是一种功能未知的蛋白质，是效应核酸酶。HamB是传感解旋酶。在监测完整双链DNA期间，HamB会限制HamA的活性。当HamAB复合物检测到DNA损伤时，HamB解旋酶活性会释放HamA，从而释放核酸酶活性。八幡激活会降解细胞中的所有DNA，产生既没有噬菌体DNA也没有宿主DNA的“幽灵”细胞。我们通过用DNA损伤剂处理证明了在没有噬菌体的情况下八幡的激活，这表明八幡对异常DNA状态有反应。八幡解旋酶与真核酶之间的系统发育相似性表明，这种细菌免疫系统已被重新用于生命所有领域的多种功能。
