Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA 94720, USA.
Cell. 2024 Nov 27;187(24):6914-6928.e20. doi: 10.1016/j.cell.2024.09.020. Epub 2024 Oct 11.
Hachiman is a broad-spectrum antiphage defense system of unknown function. We show here that Hachiman is 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 double-stranded DNA (dsDNA). When the HamAB complex detects DNA damage, HamB helicase activity activates 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 enzymes from eukaryotes and archaea suggest deep functional symmetries with other important helicases across domains of life.
八幡是一种广谱抗噬菌体防御系统，其功能未知。我们在这里表明，八幡是一种异源二聚体核酸酶-解旋酶复合物，称为 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 在监测完整双链 DNA（dsDNA）时限制 HamA 的活性。当 HamAB 复合物检测到 DNA 损伤时，HamB 解旋酶活性激活 HamA，释放核酸酶活性。八幡的激活会降解细胞中的所有 DNA，从而产生没有噬菌体和宿主 DNA 的“幻影”细胞。我们通过用 DNA 损伤剂处理来证明八幡的激活，这表明八幡对异常 DNA 状态做出反应。八幡解旋酶与真核生物和古菌中的酶之间的系统发育相似性表明，它与生命领域中的其他重要解旋酶具有深刻的功能对称性。
