| LexA DNA binding domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 lexa s119a mutant | |||||||||
| Identifiers | |||||||||
| Symbol | LexA_DNA_bind | ||||||||
| Pfam | PF01726 | ||||||||
| Pfam clan | CL0123 | ||||||||
| InterPro | IPR006199 | ||||||||
| SCOP2 | 1leb /SCOPe /SUPFAM | ||||||||
| |||||||||
TheLexA repressor orLexA (Locus for X-ray sensitivity A)[1] is a transcriptionalrepressor (EC3.4.21.88) that repressesSOS response genes coding primarily for error-proneDNA polymerases,DNA repairenzymes andcell division inhibitors.[2] LexA formsde facto atwo-component regulatory system withRecA, 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 calledautoproteolysis.[1]
LexA polypeptides contains a two domains: aDNA-binding domain and adimerization domain.[3] The dimerization domain binds to other LexA polypeptides to form dumbbell shaped dimers. The DNA-binding domain is a variant form of thehelix-turn-helix DNA bindingmotif,[4] and is usually located at theN-terminus of the protein.[1] This domain is bound to anSOS box upstream of SOS response genes until DNA damage stimulates autoproteolysis.[3]
DNA damage can be inflicted by the action ofantibiotics,bacteriophages, andUV light.[2] Of potential clinical interest is the induction of the SOS response by antibiotics, such asciprofloxacin. Bacteria requiretopoisomerases such asDNA gyrase ortopoisomerase IV forDNA replication. Antibiotics such as ciprofloxacin are able to prevent the action of these molecules by attaching themselves to the gyrate–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 becomeresistant 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 ofvirulence factors[5] andantibiotic resistance determinants,[6] as well as the activation ofintegronintegrases,[7] potentially increasing the likelihood of acquisition and dissemination of antibiotic resistance by bacteria.[2]
Impaired LexA proteolysis has been shown to interfere with ciprofloxacin resistance.[8] This offers potential forcombination therapy that combinesquinolones with strategies aimed at interfering with the action of LexA, either directly or via RecA.
| Excision repair | |
|---|---|
| Homologous recombination | |
| Other pathways | |
| Regulation | |
| Other/ungrouped | |
