|Gene:||lexA||Accession Numbers: EG10533 (EcoCyc), b4043, ECK4035|
Synonyms: exrA, spr, tsl, umuA
Subunit composition of LexA DNA-binding transcriptional repressor = [LexA]2
LexA represses the transcription of several genes involved in the cellular response to DNA damage or inhibition of DNA replication [dAri85, Fernandez00] as well as its own synthesis [Brent80]. This regulation is known as the SOS response [dAri85].
When DNA is damaged, the RecA coprotease binds to the single-stranded DNA in the damaged region to form a filament [Chen08, Cox07]. This filament interacts with the LexA dimer to activate its self-cleavage activity by an allosteric mechanism, causing the dissociation of LexA from its DNA targets and the induction of the SOS regulon for the repair of broken DNA [Giese08, Little91]. The conformational flexibility of unbound LexA is the key element in establishing a coordinated SOS response [Butala11].
LexA is widely distributed in bacteria, and it appears that it emerged from the gram-positive group [Mazon04]. It shows two domains, the N-terminal domain involved in DNA binding via a helix-turn-helix [Fogh94] and the C-terminal domain involved in dimerization and in cleavage activity [Luo01, Schnarr88].
To repress transcription, LexA blocks the access of RNA polymerase to target promoters [Little81].
LexA dimer [MohanaBorges00] recognizes and binds to an imperfect inverted repeat DNA sequence called the LexA box or SOS box [Erill03, Walker84b]. Although, the majority of the LexA-regulated genes have only one SOS box, some have two or three boxes which sometimes overlap [Gillor08].
The crystal structure of the LexA-DNA complex has been determined [Zhang10a]. The DNA-binding domains of the LexA dimer interact with the DNA in the classical fashion of a winged helix-turn-helix (HTH) motif, and they bind to the same minor groove of the DNA [Zhang10a].
The SOS system is induced by methylglyoxal (MG), based on ChIP-chip analysis with DNA-RNAP occupancy, and this involves LexA-regulated genes such as recAX, lexA-dinF, and dinB [Ozyamak13].
|Map Position: [4,255,138 -> 4,255,746] (91.71 centisomes, 330°)||Length: 609 bp / 202 aa|
Molecular Weight of Polypeptide: 22.358 kD (from nucleotide sequence)
Unification Links: ASAP:ABE-0013241 , CGSC:558 , DIP:DIP-51082N , EchoBASE:EB0528 , EcoGene:EG10533 , EcoliWiki:b4043 , Mint:MINT-1314348 , ModBase:P0A7C2 , OU-Microarray:b4043 , PortEco:lexA , PR:PRO_000023087 , Pride:P0A7C2 , Protein Model Portal:P0A7C2 , RefSeq:NP_418467 , RegulonDB:EG10533 , SMR:P0A7C2 , String:511145.b4043 , UniProt:P0A7C2
Relationship Links: InterPro:IN-FAMILY:IPR006197 , InterPro:IN-FAMILY:IPR006199 , InterPro:IN-FAMILY:IPR006200 , InterPro:IN-FAMILY:IPR011991 , InterPro:IN-FAMILY:IPR015927 , InterPro:IN-FAMILY:IPR019759 , InterPro:IN-FAMILY:IPR028360 , PDB:Structure:1JHC , PDB:Structure:1JHE , PDB:Structure:1JHF , PDB:Structure:1JHH , PDB:Structure:1LEA , PDB:Structure:1LEB , PDB:Structure:1MVD , PDB:Structure:1QAA , PDB:Structure:3JSO , PDB:Structure:3JSP , PDB:Structure:3K3R , Pfam:IN-FAMILY:PF00717 , Pfam:IN-FAMILY:PF01726 , Prints:IN-FAMILY:PR00726
In Paralogous Gene Group: 258 (2 members)
|Biological Process:||GO:0006351 - transcription, DNA-templated
[UniProtGOA11a, Brent81, Little81, Little79]
GO:0006974 - cellular response to DNA damage stimulus [UniProtGOA11a, Lin88a]
GO:0009432 - SOS response [UniProtGOA11a, GOA06, Mount72, McCall87]
GO:0045892 - negative regulation of transcription, DNA-templated [GOA06, Fernandez00]
GO:0006260 - DNA replication [UniProtGOA11a, GOA06]
GO:0006281 - DNA repair [UniProtGOA11a, GOA06]
GO:0006355 - regulation of transcription, DNA-templated [UniProtGOA11a, GOA01a]
GO:0006508 - proteolysis [GOA01a]
|Molecular Function:||GO:0003677 - DNA binding
[UniProtGOA11a, GOA06, GOA01a, Fernandez00]
GO:0004252 - serine-type endopeptidase activity [GOA06, GOA01a]
GO:0016787 - hydrolase activity [UniProtGOA11a]
|Cellular Component:||GO:0005829 - cytosol
[DiazMejia09, Ishihama08, LopezCampistrou05]
GO:0035327 - transcriptionally active chromatin
|MultiFun Terms:||cell processes → SOS response|
|information transfer → DNA related → DNA repair|
|information transfer → RNA related → Transcription related|
|regulation → genetic unit regulated → regulon|
|regulation → type of regulation → transcriptional level → repressor|
DNA binding site length: 20 base-pairs
Symmetry: Inverted Repeat
Consensus DNA Binding Sequence: TACTGTATATATATACAGTA
|Growth Medium||Growth?||T (°C)||O2||pH||Osm/L||Growth Observations|
|LB Lennox||No||37||Aerobic||7||No [Baba06, Comment 1]|
|DNA-Binding-Region||28 -> 48|
10/20/97 Gene b4043 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10533.
Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554
Blattner93: Blattner FR, Burland V, Plunkett G, Sofia HJ, Daniels DL (1993). "Analysis of the Escherichia coli genome. IV. DNA sequence of the region from 89.2 to 92.8 minutes." Nucleic Acids Res 1993;21(23);5408-17. PMID: 8265357
Butala11: Butala M, Klose D, Hodnik V, Rems A, Podlesek Z, Klare JP, Anderluh G, Busby SJ, Steinhoff HJ, Zgur-Bertok D (2011). "Interconversion between bound and free conformations of LexA orchestrates the bacterial SOS response." Nucleic Acids Res 39(15);6546-57. PMID: 21576225
DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114
Erill03: Erill I, Escribano M, Campoy S, Barbe J (2003). "In silico analysis reveals substantial variability in the gene contents of the gamma proteobacteria LexA-regulon." Bioinformatics 19(17);2225-36. PMID: 14630651
Fernandez00: Fernandez De Henestrosa AR, Ogi T, Aoyagi S, Chafin D, Hayes JJ, Ohmori H, Woodgate R (2000). "Identification of additional genes belonging to the LexA regulon in Escherichia coli." Mol Microbiol 35(6);1560-72. PMID: 10760155
Fogh94: Fogh RH, Ottleben G, Ruterjans H, Schnarr M, Boelens R, Kaptein R (1994). "Solution structure of the LexA repressor DNA binding domain determined by 1H NMR spectroscopy." EMBO J 1994;13(17);3936-44. PMID: 8076591
Kreuzer13: Kreuzer KN (2013). "DNA damage responses in prokaryotes: regulating gene expression, modulating growth patterns, and manipulating replication forks." Cold Spring Harb Perspect Biol 5(11);a012674. PMID: 24097899
Lamerichs89: Lamerichs RM, Padilla A, Boelens R, Kaptein R, Ottleben G, Ruterjans H, Granger-Schnarr M, Oertel P, Schnarr M (1989). "The amino-terminal domain of LexA repressor is alpha-helical but differs from canonical helix-turn-helix proteins: a two-dimensional 1H NMR study." Proc Natl Acad Sci U S A 1989;86(18);6863-7. PMID: 2780544
LopezCampistrou05: Lopez-Campistrous A, Semchuk P, Burke L, Palmer-Stone T, Brokx SJ, Broderick G, Bottorff D, Bolch S, Weiner JH, Ellison MJ (2005). "Localization, annotation, and comparison of the Escherichia coli K-12 proteome under two states of growth." Mol Cell Proteomics 4(8);1205-9. PMID: 15911532
Luo01: Luo Y, Pfuetzner RA, Mosimann S, Paetzel M, Frey EA, Cherney M, Kim B, Little JW, Strynadka NC (2001). "Crystal structure of LexA: a conformational switch for regulation of self-cleavage." Cell 106(5);585-94. PMID: 11551506
McCall87: McCall JO, Witkin EM, Kogoma T, Roegner-Maniscalco V (1987). "Constitutive expression of the SOS response in recA718 mutants of Escherichia coli requires amplification of RecA718 protein." J Bacteriol 169(2);728-34. PMID: 3542969
Miki81: Miki T, Ebina Y, Kishi F, Nakazawa A (1981). "Organization of the lexA gene of Escherichia coli and nucleotide sequence of the regulatory region." Nucleic Acids Res 1981;9(3);529-43. PMID: 6261224
MohanaBorges00: Mohana-Borges R, Pacheco AB, Sousa FJ, Foguel D, Almeida DF, Silva JL (2000). "LexA repressor forms stable dimers in solution. The role of specific dna in tightening protein-protein interactions." J Biol Chem 275(7);4708-12. PMID: 10671501
Mount72: Mount DW, Low KB, Edmiston SJ (1972). "Dominant mutations (lex) in Escherichia coli K-12 which affect radiation sensitivity and frequency of ultraviolet lght-induced mutations." J Bacteriol 112(2);886-93. PMID: 4343824
Ozyamak13: Ozyamak E, de Almeida C, de Moura AP, Miller S, Booth IR (2013). "Integrated stress response of Escherichia coli to methylglyoxal: transcriptional readthrough from the nemRA operon enhances protection through increased expression of glyoxalase I." Mol Microbiol. PMID: 23646895
Schnarr88: Schnarr M, Granger-Schnarr M, Hurstel S, Pouyet J (1988). "The carboxy-terminal domain of the LexA repressor oligomerises essentially as the entire protein." FEBS Lett 234(1);56-60. PMID: 2968919
Lewis94: Lewis LK, Harlow GR, Gregg-Jolly LA, Mount DW (1994). "Identification of high affinity binding sites for LexA which define new DNA damage-inducible genes in Escherichia coli." J Mol Biol 241(4);507-23. PMID: 8057377
©2014 SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025-3493