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

The ability to sense DNA damage and activate DNA damage response pathways is critical for repairing DNA damage in all domains of life. The most well studied pathway for DNA damage repair (DDR) in bacteria includes the "save our souls" (SOS) pathway, although many components of this pathway are missing in the Acinetobacter clade. One aspect of DDR pathways includes the inhibition of cell division to prevent the inheritance of damaged DNA by daughter cells, the mechanism of which is also unknown in Acinetobacter. In this work, we show the cell filamentation factor AciT acts as a cell division inhibitor that confers a fitness advantage in the presence of DNA damage-inducing agents. Suppressor mutations that permit cell viability in conditions with constitutively active AciT mapped to a WYL family transcriptional regulator, DdaA, which we demonstrate acts as an activator of aciT expression. DdaA was also found to activate DDR pathway gene expression including recA via a conserved mechanism used by WYL family homologues to sense and respond to DNA damage. We further demonstrate that DdaA activates the expression of DDR pathway genes upon DNA uptake during natural transformation, identifying a new mechanism for how transcriptional control networks intersect to regulate bacterial responses in diverse environmental contexts.