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Updated: Feb 13, 2026

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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
PubMed

Insights

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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