The transcriptional regulator LexA functions as a repressor of the bacterial SOS response, which is induced under DNA-damaging conditions. This results in the expression of genes important for survival and adaptation.

DNA damage often causes an arrest of the cell cycle that provides time for genome integrity to be restored. In bacteria, the classical SOS DNA damage response leads to an inhibition of cell division resulting in temporarily filamentous growth. This raises the question as to whether such a response mechanism might similarly function in naturally filamentous bacteria such as Streptomyces. Streptomyces exhibit two functionally distinct forms of cell division: cross-wall formation in vegetative hyphae and sporulation septation in aerial hyphae. Here, we show that the genotoxic agent mitomycin C confers a block in sporulation septation in Streptomyces venezuelae in a mechanism that involves, at least in part, the downregulation of ssgB. Notably, this DNA damage response does not appear to block cross-wall formation and may be independent of canonical SOS and developmental regulators. We also show that the mitomycin C-induced block in sporulation can be partially bypassed by the constitutive expression of ssgB, though this appears to be largely limited to mitomycin C treatment and the resultant spore-like cells have reduced viability.

DNA damage triggers a widely conserved stress response in bacteria called the SOS response that involves two key regulators, the activator RecA and the transcriptional repressor LexA. Despite the wide conservation of the SOS response, the number of genes controlled by LexA varies considerably between different organisms. The filamentous soil-dwelling bacteria of the genus Streptomyces contain LexA and RecA homologs but their rolesin Streptomyces have not been systematically studied. Here, we demonstrate that RecA and LexA are required for the survival of Streptomyces venezuelae during DNA damaging conditions and for normal development during unperturbed growth. Monitoring the activity of a fluorescent recA promoter fusion and LexA protein levels revealed that the activation of the SOS response is delayed in S. venezuelae. By combining global transcriptional profiling and ChIP-seq analysis, we determined the LexA regulon and defined the core set of DNA damage repair genes that are expressed in response to treatment with the DNA alkylating agent mitomycin C. Our results show that DNA damage-induced degradation of LexA results in the differential regulation of LexA target genes. Using Surface Plasmon Resonance, we further confirm the LexA DNA binding motif (SOS box) and demonstrate that LexA displays tight but distinct binding affinities to its target promoters, indicating a graded response to DNA damage.