Hachiman is a genome integrity sensor.
Hachiman is a genome integrity sensor.
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Hachiman 是一种基因组完整性传感器。
DOI：
10.1101/2024.02.29.582594
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Doudna,JenniferA
中科院分区：
文献类型：
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作者：
Tuck,OwenT;Adler,BenjaminA;Armbruster,EmilyG;Lahiri,Arushi;Hu,JasonJ;Zhou,Julia;Pogliano,Joe;Doudna,JenniferA
Hachiman是一种功能未知的广谱抗噬菌体防御系统。我们在这里表明，八幡包括一个异二聚体核酸酶解旋酶复合物，HamAB。HamA，以前是一种功能未知的蛋白质，是效应核酸酶。HamB是传感器解旋酶。HamB在完整dsDNA的监测期间抑制HamA活性。当HamAB复合物检测到DNA损伤时，HamB解旋酶活性释放HamA，释放核酸酶活性。Hachiman激活降解细胞中的所有DNA，产生缺乏噬菌体和宿主DNA的“幻影”细胞。我们证明了八奇满激活的情况下，噬菌体的DNA损伤剂的治疗，表明八奇满响应异常的DNA状态。Hachiman解旋酶和真核生物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利用，在生命的所有领域发挥不同的功能。
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.