Genome integrity sensing by the broad-spectrum Hachiman antiphage defense complex
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.
Authors
- Joe Pogliano (ORCID: https://orcid.org/0000-0001-8989-2655)
- Arushi Lahiri (ORCID: https://orcid.org/0000-0001-6834-4692)
- Jason J. Hu (ORCID: https://orcid.org/0000-0002-1103-2177)
- Owen T. Tuck (ORCID: https://orcid.org/0000-0002-0348-6910)
- Julia Zhou (ORCID: https://orcid.org/0000-0003-4084-0269)
- Emily G. Armbruster (ORCID: https://orcid.org/0000-0003-0377-1209)
- Jennifer A. Doudna (ORCID: https://orcid.org/0000-0001-9161-999X)
- Benjamin A. Adler (ORCID: https://orcid.org/0000-0002-7488-3040)
Institutions
- QB3 (US)
- Gladstone Institutes (US)
- Howard Hughes Medical Institute (US)
- Lawrence Berkeley National Laboratory (US)
- University of California, San Francisco (US)
- University of California San Diego (US)
- Innovative Genomics Institute (US)
- University of California, Berkeley (US)
Publication Details
- Journal
- Cell
- Published
- 2024-10-11
- DOI
- https://doi.org/10.1016/j.cell.2024.09.020
- Citations
- 29
- Primary Topic
- DNA Repair Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 6.78
Funders
- National Science Foundation
- Foundation for the National Institutes of Health
- Howard Hughes Medical Institute
- U.S. Department of Energy
- Innovative Genomics Institute
- Emerson Collective
- National Institutes of Health
- Directorate for Biological Sciences
- Office of Science
- National Heart, Lung, and Blood Institute
- National Institute of Allergy and Infectious Diseases
- National Institute of Neurological Disorders and Stroke
- Biological and Environmental Research
- Lawrence Livermore National Laboratory
- Lawrence Berkeley National Laboratory