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A WYL transcriptional regulator activates the DNA damage response pathway in Acinetobacter species

Taylor J Ellison1, Taylor A Smith1, Neha Vennapusa1

  • 1Department of Microbiology, University of Georgia, Athens, GA 30602, United States.

Nucleic Acids Research
|March 24, 2026
PubMed

Insights

Bacteria sense DNA damage using the AciT cell division inhibitor. A WYL family regulator, DdaA, activates AciT and DNA damage response genes, revealing a new bacterial damage response mechanism.

Area of Science:

  • Bacterial genetics and molecular biology
  • DNA damage response mechanisms
  • Cell division regulation

Background:

  • DNA damage sensing and repair are vital for all life.
  • The Acinetobacter clade lacks key components of the canonical bacterial DNA damage response (DDR) pathway.
  • Mechanisms of cell division inhibition during DDR are unknown in Acinetobacter.

Purpose of the Study:

  • To investigate the role of the cell filamentation factor AciT in bacterial DNA damage response.
  • To identify regulators of AciT and explore their function in DDR.
  • To elucidate novel mechanisms of bacterial response to DNA damage and environmental cues.

Main Methods:

  • Genetic analysis of suppressor mutations.
  • Gene expression analysis (e.g., recA activation).
  • Phenotypic analysis of bacterial growth and cell division under DNA-damaging conditions.

Main Results:

  • AciT functions as a cell division inhibitor, providing a fitness advantage under DNA damage.
  • The WYL family transcriptional regulator DdaA activates aciT expression.
  • DdaA activates DDR genes, including recA, through a conserved WYL domain mechanism.
  • DdaA also induces DDR gene expression during natural transformation (DNA uptake).

Conclusions:

  • AciT is a key player in Acinetobacter's response to DNA damage by inhibiting cell division.
  • DdaA acts as a DNA damage sensor and transcriptional activator, linking environmental sensing to DDR.
  • This study reveals a novel intersection of transcriptional networks regulating bacterial responses in diverse contexts.

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