Repressor lexA

Repressor LexA or LexA is a transcriptional repressor (EC 3.4.21.88) that represses SOS response genes coding primarily for error-prone DNA polymerases, DNA repair enzymes and cell division inhibitors. LexA forms de facto a two-component regulatory system with RecA, which senses DNA damage at stalled replication forks, forming monofilaments and acquiring an active conformation capable of binding to LexA and causing LexA to cleave itself, in a process called autoproteolysis.

DNA damage can be inflicted by the action of antibiotics, bacteriophages and UV light. Of potential clinical interest is the induction of the SOS response by antibiotics, such as ciprofloxacin. Bacteria require topoisomerases such as DNA gyrase or topoisomerase IV for DNA replication. Antibiotics such as ciprofloxacin are able to prevent the action of these molecules by attaching themselves to the gyrase - DNA complex, leading to replication fork stall and the induction of the SOS response. The expression of error-prone polymerases under the SOS response increases the basal mutation rate of bacteria. While mutations are often lethal to the cell, they can also enhance survival. In the specific case of topoisomerases, some bacteria have mutated one of their amino acids so that the ciprofloxacin can only create a weak bond to the topoisomerase. This is one of the methods that bacteria use to become resistant to antibiotics. Ciprofloxacin treatment can therefore potentially lead to the generation of mutations that may render bacteria resistant to ciprofloxacin. In addition, ciprofloxacin has also been shown to induce via the SOS response dissemination of virulence factors and antibiotic resistance determinants, as well as the activation of integron integrases, potentially increasing the likelihood of acquisition and dissemination of antibiotic resistance by bacteria.

Impaired LexA proteolysis has been shown to interfere with ciprofloxacin resistance. This offers potential for combination therapy that combines quinolones with strategies aimed at interfering with the action of LexA, either directly or via RecA.

LexA contains a DNA binding domain. The winged HTH motif of LexA is a variant form of the helix-turn-helix DNA binding motif. it is usually located at the N-terminus of the protein.