The SOS response is governed by the transcriptional regulator LexA and is elicited in many bacterial species in response to DNA damaging conditions. Induction of the SOS response is mediated by autocleavage of the LexA repressor resulting in a C-terminal dimerization domain (CTD) and an N-terminal DNA-binding domain (NTD) known to retain some DNA-binding activity. The proteases responsible for degrading the LexA domains have been identified in Escherichia coli as ClpXP and Lon. Here, we show that in the human and animal pathogen Staphylococcus aureus, the ClpXP and ClpCP proteases contribute to degradation of the NTD and to a lesser degree the CTD. In the absence of the proteolytic subunit, ClpP, or one or both of the Clp ATPases, ClpX and ClpC, the LexA domains were stabilized after autocleavage. Production of a stabilized variant of the NTD interfered with mitomycin-mediated induction of sosA expression while leaving lexA unaffected, and also significantly reduced SOS-induced mutagenesis. Our results show that sequential proteolysis of LexA is conserved in S. aureus and that the NTD may differentially regulate a subset of genes in the SOS regulon.
Bacteriophage GIL01 gp7 interacts with host LexA repressor to enhance DNA binding and inhibit RecA-mediated auto-cleavage
