Hachiman is a genome integrity sensor.
| Autor: | Tuck OT; Department of Chemistry, University of California, Berkeley, Berkeley, CA USA.; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA USA., Adler BA; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA USA.; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA USA., Armbruster EG; School of Biological Sciences, University of California San Diego, La Jolla, CA USA., Lahiri A; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California USA., Hu JJ; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California USA., Zhou J; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California USA., Pogliano J; School of Biological Sciences, University of California San Diego, La Jolla, CA USA., Doudna JA; Department of Chemistry, University of California, Berkeley, Berkeley, CA USA.; Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA USA.; California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA USA.; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California USA.; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA USA.; MBIB Division, Lawrence Berkeley National Laboratory, Berkeley, CA USA.; Gladstone Institutes, University of California, San Francisco, San Francisco, CA USA.; Department of Bioengineering, University of California, Berkeley, Berkeley, CA USA. |
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| Jazyk: | angličtina |
| Zdroj: | BioRxiv : the preprint server for biology [bioRxiv] 2024 Feb 29. Date of Electronic Publication: 2024 Feb 29. |
| DOI: | 10.1101/2024.02.29.582594 |
| Abstrakt: | 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. Competing Interests: Competing interest statement J.A.D. is a co-founder of Caribou Biosciences, Editas Medicine, Intellia Therapeutics, Mammoth Biosciences and Scribe Therapeutics, and a director of Altos, Johnson & Johnson and Tempus. J.A.D. is a scientific advisor to Caribou Biosciences, Intellia Therapeutics, Mammoth Biosciences, Inari, Scribe Therapeutics, Felix Biosciences and Algen. J.A.D. also serves as Chief Science Advisor to Sixth Street and a Scientific Advisory Board member at The Column Group. J.A.D. conducts academic research projects sponsored by Roche and Apple Tree Partners. J.P. has an equity interest in Linnaeus Bioscience Incorporated and receives income. The terms of this arrangement have been reviewed and approved by the University of California, San Diego, in accordance with its conflict-of-interest policies. |
| Databáze: | MEDLINE |
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