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 repairenzymes 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 integronintegrases,[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.
^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. PMC1088971. 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. PMC395313. PMID 8076591.
This article incorporates text from the public domain Pfam and InterPro: IPR006199
repressor, lexa, repressor, lexa, lexa, locus, sensitivity, transcriptional, repressor, that, represses, response, genes, coding, primarily, error, prone, polymerases, repair, enzymes, cell, division, inhibitors, lexa, forms, facto, component, regulatory, syst. 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 LexA DNA binding domainlexa s119a mutantIdentifiersSymbolLexA DNA bindPfamPF01726Pfam clanCL0123InterProIPR006199SCOP21leb SCOPe SUPFAMAvailable protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summaryDNA 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 References edit Butala M Zgur 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 a b c Erill 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 a b Butala 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 Penades 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 Beaber JW Hochhut B Waldor MK 2004 SOS response promotes horizontal dissemination of antibiotic resistance genes Nature 427 6969 72 74 Bibcode 2004Natur 427 72B doi 10 1038 nature02241 PMID 14688795 S2CID 4300746 Guerin E Cambray G Sanchez Alberola N Campoy S Erill I Da Re S Gonzalez Zorn B Barbe 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 This article incorporates text from the public domain Pfam and InterPro IPR006199 Portal nbsp Biology Retrieved from https en wikipedia org w index php title Repressor lexA amp oldid 1188108444, wikipedia, wiki, book, books, library,
