Repressor LexA or LexA (Locus for X-ray sensitivity A)[1] 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.[2] 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.[3]
DNA damage can be inflicted by the action of antibiotics, bacteriophages, and UV light.[2] 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 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 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 [4] and antibiotic resistance determinants,[5] as well as the activation of integron integrases,[6] 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.[7] 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,[8] and it is usually located at the N-terminus of the protein.[3]
^Butala, M.; Žgur-Bertok, D.; Busby, S. J. W. (January 2009). "The bacterial LexA transcriptional repressor". Cellular and Molecular Life Sciences. 66 (1): 82–93. doi:10.1007/s00018-008-8378-6. ISSN 1420-682X. PMID 18726173. S2CID 29537019.
^ abcErill I, Campoy S, Barbe J (2007). "Aeons of distress: an evolutionary perspective on the bacterial SOS response". FEMS Microbiol. Rev. 31 (6): 637–656. doi:10.1111/j.1574-6976.2007.00082.x. PMID 17883408.
^ abButala M, Zgur-Bertok D, Busby SJ (2009). "The bacterial LexA transcriptional repressor". Cell Mol Life Sci. 66 (1): 82–93. doi:10.1007/s00018-008-8378-6. PMID 18726173. S2CID 29537019.
^Ubeda C, Maiques E, Knecht E, Lasa I, Novick RP, Penadés JR (2005). "Antibiotic-induced SOS response promotes horizontal dissemination of pathogenicity island-encoded virulence factors in staphylococci". Mol. Microbiol. 56 (3): 836–844. doi:10.1111/j.1365-2958.2005.04584.x. PMID 15819636.
^Guerin E, Cambray G, Sanchez-Alberola N, Campoy S, Erill I, Da Re S, Gonzalez-Zorn B, Barbé J, Ploy MC, Mazel D (2009). "The SOS response controls integron recombination". Science. 324 (5930): 1034. Bibcode:2009Sci...324.1034G. doi:10.1126/science.1172914. PMID 19460999. S2CID 42334786.
^Cirz RT, Chin JK, Andes DR, et al. (2005). "Inhibition of mutation and combating the evolution of antibiotic resistance". PLOS Biol. 3 (6): e176. doi:10.1371/journal.pbio.0030176. PMC 1088971. PMID 15869329.
^Fogh RH, Ottleben G, Ruterjans H, Schnarr M, Boelens R, Kaptein R (September 1994). "Solution structure of the LexA repressor DNA binding domain determined by 1H NMR spectroscopy". EMBO J. 13 (17): 3936–44. doi:10.1002/j.1460-2075.1994.tb06709.x. PMC 395313. PMID 8076591.
RepressorLexA or LexA (Locus for X-ray sensitivity A) is a transcriptional repressor (EC 3.4.21.88) that represses SOS response genes coding primarily...
stimulated by single-stranded DNA, is involved in the inactivation of the repressor (LexA) of SOS response genes thereby inducing the response. It is an error-prone...
Lexa in Wiktionary, the free dictionary. Lexa may refer to: Lexa, Arkansas, a city in Phillips County, United States RepressorlexALexa (name) Lexa (singer)...
Transcription of the SOS response genes is negatively regulated by the LexArepressor. LexA binds to the promoter of the UmuDC operon and inhibits gene transcription...
the SOS response: lexA encodes a repressor for all the genes in the system, and recA encodes a protein able to cleave the LexArepressor upon activation...
is the region in the promoter of various genes to which the LexArepressor binds to repress the transcription of SOS-induced proteins. This occurs in the...
representation as a sequence logo. PSFM for the transcriptional repressorLexA as derived from 56 LexA-binding sites stored in Prodoric. Relative frequencies are...
RecA stimulates the autoproteolysis of the SOS transcriptional repressorLexA. The LexA regulon includes a cell division inhibitor, SulA, that prevent...
he cloned the E. coli LexArepressor and showed how it controlled the cell's response to DNA damage, used LexA as a repressor in yeast, and created fusion...
co-protease function in the autocatalytic cleavage of the LexArepressor and the λ repressor. RecA's association with DNA repair is based on its central...
activate LexA autoprotease activity, which ultimately leads to cleavage of LexA dimer and subsequent LexA degradation. The loss of LexArepressor induces...
repressive decisions agreed at ministerial level, including the decision to repress the peaceful demonstrations on 19 December 2010. After December 2010, he...
motifs for the SOS transcriptional repressor, and shown that SOS networks can be regulated by transcriptional repressors encoded by bacteriophages. Erill's...
freedom of peaceful assembly and of association, in particular by violently repressing protests and demonstrations." These relate to the quelling of pro-Navalny...
in the intricate domain of motif discovery. The E. coli lactose operon repressor LacI (PDB: 1lcc chain A) and E. coli catabolite gene activator (PDB:...
support for him. Two days after Warsaw Pact invasion of Czechoslovakia to repress the Prague Spring, Castro took to the airwaves and publicly denounced the...
title assigned by the Statute Law Revision Act 1948 "New River Act 1605". vLex. Pickering, Danby, ed. (1763). The Statutes at Large. Vol. 7: From the Thirty-ninth...
reporter gene preceded by five LexAOp sequences. In the C2H system the bait plasmid (pC2HB) contains the Staphylococcus aureus LexA BD, while the prey plasmid...
HES1. Expression of this hairy-like bHLH transcription factor, which represses Neurogenin but is required for Ascl1, is progressively lost from the caudal...
lethal mutation near the GAL80 site. Dual-expression control MARCM uses the LexA-VP16 transcriptional system in concordance with GAL4-UAS. MARCM is also often...