A DNA damage-activated kinase controls bacterial immune pathway expression.
Lydia R Chambers1, Phoolwanti Rani2,3, Ryan K Min2
1Department of Biochemistry and Molecular Biophysics, University of California San Diego, La Jolla CA 92093 USA.
Biorxiv : the Preprint Server for Biology
|February 12, 2026
Summary
Bacteria use CapK and CapS proteins to regulate immune pathways in response to DNA damage. This kinase-substrate pair controls gene expression and is integrated into anti-phage systems, demonstrating pathway modularity.
Area of Science:
- Microbiology
- Molecular Biology
- Bacterial Genetics
Background:
- Bacteria possess diverse stress-response pathways crucial for host defense.
- Regulation of anti-phage immune pathways, particularly those involving host cell killing, remains a key research area.
Purpose of the Study:
- To identify and characterize proteins regulating bacterial immune operons in response to DNA damage.
- To elucidate the mechanism by which these proteins control gene expression and their role in stress response.
Main Methods:
- Protein characterization (CapK and CapS) and their genetic loci.
- Biochemical assays to determine kinase activity and DNA-binding properties.
- Analysis of gene expression regulation and integration into toxin-antitoxin systems.
Main Results:
- Identified CapK (kinase) and CapS (DNA-binding repressor) proteins regulating immune operons.
- Phosphorylation of CapS by CapK leads to de-repression of transcription, activated by single-stranded DNA.
- Demonstrated co-option of CapK/CapS into an anti-phage toxin-antitoxin system, linking DNA damage to VapC nuclease activation.
Conclusions:
- A kinase-substrate pair (CapK-CapS) regulates adjacent operons in response to DNA damage.
- Revealed the modular nature of bacterial immune and stress-response pathways, adaptable for different cellular threats.
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