Activation of bacterial response to DNA damage

Matej Butala

Department of Biology, Biotehnical Faculty, University of Ljubljana

Abstract: Bacteria respond to DNA damage by mounting a coordinated cellular response governed by the RecA and LexA proteins. In Escherichia coli RecA stimulates cleavage of the LexA repressor inducing more than 40 genes that comprise the SOS global regulatory network. Induction of the SOS response modulates evolution and dissemination of drug resistance, as well as synthesis, secretion and dissemination of virulence factors of some well characterised pathogens.
By molecular dynamic simulations we revealed that LexA repressor can switch between DNA binding and DNA non-binding conformation. This was confirmed with in vitro experiments that exploited cysteine crosslinking. We provide novel insight that LexA conformations affect RecA-mediated cleavage, therefore affect activation of the SOS response. As some antibiotics, can instigate the SOS response, investigation of the LexA protein may provide new directions in the battle against the emergence and spread of drug resistance.