The bacterial LexA transcriptional repressor

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. The SOS response is widespread among bacteria and exhibits considerable variation in its composition and regulation. In some well-characterised pathogens, induction of the SOS response modulates the evolution and dissemination of drug resistance, as well as synthesis, secretion and dissemination of the virulence. In this review, we discuss the structure of LexA protein, particularly with respect to distinct conformations that enable repression of SOS genes via specific DNA binding or repressor cleavage during the response to DNA damage. These may provide new starting points in the battle against the emergence of bacterial pathogens and the spread of drug resistance among them.

Genetic makeup of the Corynebacterium glutamicum LexA regulon deduced from comparative transcriptomics and in vitro DNA band shift assays

“…The underlying gene regulatory network is controlled by a complex interplay involving the LexA and RecA proteins (Friedberg et al, 2005;Little & Mount, 1982). Under normal growth conditions LexA binds as a dimer to specific operators, termed SOS boxes, thereby repressing the transcription of SOS genes by sterically occluding binding of RNA polymerase to the promoter (Brent & Ptashne, 1981;Little et al, 1981;Butala et al, 2009). Exposure of the cell to agents or conditions that damage DNA induces the SOS response by binding of RecA to regions of single-stranded DNA that arise from blocked replication forks or during processing of damaged DNA (Sassanfar & Roberts, 1990).…”

Gene transcription from the linear plasmid pBClin15 leads to cell lysis and extracellular DNA-dependent aggregation of Bacillus cereus ATCC 14579 in response to quinolone-induced stress

“…Persister cell formation has been described to occur in E. coli when challenged with the fluoroquinolone ciprofloxacin (Dörr et al, 2009), a process that was inducible and dependent on the SOS response. The SOS response is a DNA damage repair system that is induced as a result of stalled replication forks and hence characteristically activated during quinolone stress (Butala et al, 2009). In addition to being a cellular DNA repair system, induction of the SOS response is a mechanism that commonly leads to phage activation.…”

The checkpoint transcriptional response: Make sure to turn it off once you are satisfied

“…[46][47][48] with the replication stress and shares similarities with transcriptional repression mechanisms found in bacteria and mammals. 15,16 Our recent discovery of a select group of CC promoter genes that undergo a transcriptional factor switch during the G 1 -to-S transition (which we named the "switch genes") further illustrates the need for tight control of replication stressinduced genes.…”

“…In E. coli, LexA mediates feedback regulation during the SOS response and mammalian Mdm2, a negative regulator of p53, mediates feedback regulation of transcription during recovery from the DNA damage checkpoint response. 15,16 The conservation of this particular network wiring shows that the transcriptional response initiated by DNA damage and replication stress needs to be rapidly repressed once those problems have been rectified.…”