|Gene:||uvrC||Accession Numbers: EG11063 (EcoCyc), b1913, ECK1912|
Component of: UvrABC Nucleotide Excision Repair Complex (extended summary available)
UvrC is one of three (along with UvrA and UvrB) enzyme components participating in the nucleotide excision repair (NER) process. The NER generalized DNA repair process repairs a wide variety of DNA lesions.
Gene Citations: [Moolenaar87]
|Map Position: [1,990,898 <- 1,992,730] (42.91 centisomes, 154°)||Length: 1833 bp / 610 aa|
Molecular Weight of Polypeptide: 68.188 kD (from nucleotide sequence)
Unification Links: ASAP:ABE-0006370 , CGSC:19 , DIP:DIP-47875N , EchoBASE:EB1056 , EcoGene:EG11063 , EcoliWiki:b1913 , Mint:MINT-1221235 , ModBase:P0A8G0 , OU-Microarray:b1913 , PortEco:uvrC , PR:PRO_000024200 , Pride:P0A8G0 , Protein Model Portal:P0A8G0 , RefSeq:NP_416423 , RegulonDB:EG11063 , SMR:P0A8G0 , String:511145.b1913 , Swiss-Model:P0A8G0 , UniProt:P0A8G0
Relationship Links: InterPro:IN-FAMILY:IPR000305 , InterPro:IN-FAMILY:IPR000445 , InterPro:IN-FAMILY:IPR001162 , InterPro:IN-FAMILY:IPR001943 , InterPro:IN-FAMILY:IPR003583 , InterPro:IN-FAMILY:IPR004791 , InterPro:IN-FAMILY:IPR010994 , InterPro:IN-FAMILY:IPR027299 , PDB:Structure:1KFT , Pfam:IN-FAMILY:PF00633 , Pfam:IN-FAMILY:PF01541 , Pfam:IN-FAMILY:PF02151 , Pfam:IN-FAMILY:PF08459 , Prosite:IN-FAMILY:PS50151 , Prosite:IN-FAMILY:PS50164 , Prosite:IN-FAMILY:PS50165 , Smart:IN-FAMILY:SM00278 , Smart:IN-FAMILY:SM00465
In Paralogous Gene Group: 361 (2 members)
|Biological Process:||GO:0000737 - DNA catabolic process, endonucleolytic
GO:0006281 - DNA repair [UniProtGOA11a, GOA01a]
GO:0006289 - nucleotide-excision repair [GOA06]
GO:0006974 - cellular response to DNA damage stimulus [UniProtGOA11a]
GO:0009432 - SOS response [UniProtGOA11a, GOA06]
|Molecular Function:||GO:0003677 - DNA binding
GO:0004518 - nuclease activity [UniProtGOA11a]
GO:0009381 - excinuclease ABC activity [GOA06, GOA01a]
|Cellular Component:||GO:0009380 - excinuclease repair complex
GO:0005737 - cytoplasm [UniProtGOA11, UniProtGOA11a, GOA06, GOA01a]
GO:0005829 - cytosol [DiazMejia09]
|MultiFun Terms:||cell processes → protection → radiation|
|information transfer → DNA related → DNA degradation|
|information transfer → DNA related → DNA repair|
|metabolism → degradation of macromolecules → DNA|
|Growth Medium||Growth?||T (°C)||O2||pH||Osm/L||Growth Observations|
|LB enriched||Yes||37||Aerobic||6.95||Yes [Gerdes03, Comment 1]|
|LB Lennox||Yes||37||Aerobic||7||Yes [Baba06, Comment 2]|
|M9 medium with 1% glycerol||Yes||37||Aerobic||7.2||0.35||Yes [Joyce06, Comment 3]|
|MOPS medium with 0.4% glucose||Yes||37||Aerobic||7.2||0.22||Yes [Baba06, Comment 2]|
Subunit of: UvrABC Nucleotide Excision Repair Complex
Synonyms: excinuclease ABC, UvrABC excinuclease, excinuclease UvrABC, excision nuclease ABC, UvrABC system excision endonuclease, ABC excision nuclease
Subunit composition of
UvrABC Nucleotide Excision Repair Complex = [UvrB][UvrC][UvrA]
DNA repair; excision nuclease subunit B = UvrB (summary available)
excinuclease ABC, subunit C; repair of UV damage to DNA = UvrC (summary available)
excision nuclease subunit A = UvrA (summary available)
Nucleotide excision repair (NER) is a generalized DNA repair process which can repair a wide diversity of DNA lesion including UV-induced photoproducts (cyclobutane dimers, 6-4 photoproducts, thymine glycol), bulky adducts, apurininc/apyrimidinic (AP) sites and cross-links. While some of these are also repaired by other pathways, in most cases NER is the major pathway for their repair. The nucleotide excision repair pathway consists of the following steps: recognition of the damaged area; incision 3' and 5' to the damaged area; excision of the lesion-containing oligonucleotide; resynthesis of the excised strand and ligation to form a repaired duplex. The main constituents of the pathway are the products of the genes uvrA, uvrB and uvrC [Lin89].
Recognition of the damaged region is carried out in E. coli by UvrA which has been found to exist as a monomer in the absence of ATP but in the presence of ATP it forms homodimers [Sancar88]. The most stable dimer of UvrA contains a mixture of ADP and ATP which is formed upon hydrolysis [Wagner09] although other studies have shown that UvrA dimerization is stimulated by ATP binding but not hydrolysis [Oh89]. UvrA contains two ATP binding sites and three other structural motifs-- two zinc fingers and a helix-turn-helix motif, which are thought to be required for the proper recognition of damaged DNA substrate [Wang93]. UvrA binds DNA as a dimer with a strong preference for DNA ends [Wagner09].
In vitro studies at physiological concentrations show that UvrA associates with UvrB to form a (UvrA2)UvrB complex in an ATP-dependent interaction [Orren89]. The complex has been shown to have a higher binding affinity for damaged DNA than for undamaged DNA [Sancar88]. Purification studies of the complex binding characteristics [Oh86] suggest that the UvrA2B complex tracks along the DNA until a damage site is located. Experimental evidence [Zou99] strongly suggests that UvrA2B complex possesses a helicase activity allowing it to unwind the double stranded DNA permitting access to the adduct by UvrB resulting in dynamic damage recognition and subsequent UvrB binding.
UvrC protein has a high affinity for the UvrB-DNA complex (the UvrA subunits having dissociated concomitant with damage site recognition and attachment). The UvrC protein is the endonucleolytic component of the nucleotide excision complex and it consists of two functional parts with the N-terminal half containing the 3' incision catalytic domain incising first after which the C-terminal half containing the 5' incision catalytic domain performs the second incision [Sancar88]. The UvrD helicase (helicase II) has been implicated in removal of the lesion-containing oligonucleotide and disassembly of the repair complex [Orren92]. An additional endonuclease (the ydjQ gene product-or Cho for UvrC Homologue) has been shown to share significant sequence homology with the N-terminal half of UvrC [Moolenaar02] and is capable of even more efficient 3' incision than UvrC.
In E. coli, NER occurs at a higher rate on the transcribed strand of actively transcribed genes (compared to the non-transcribed strand of the same gene or non-transcribed regions of the genome). This transcription-coupled repair (TCR) activity has been ascribed to a protein called the 'transcription-repair coupling factor' which in E.coli is the product of the mfd (mutation frequency decline) gene [Selby93]. A second pathway for TCR, involving the DNA helicase protein UvrD has also been characterised in E. coli K-12. In this pathway UvrD, in conjuction with NusA, clears lesions by forcing obstructed elongation complexes to backtrack, allowing UvrABC to gain access to damaged sites [Epshtein14]. UvrD mediated TCR facilitates NER without the loss of RNA polymerase which enables prompt resumption of transcription [Epshtein14].
UvrA is one of a series of genes known as SOS genes which, in the event of DNA damage and other stresses, are induced to increased transcription levels. UvrA is constitutively expressed in E. coli at a level of ~ 25 molecules per cell but SOS-mediated induction of its gene increases the level to ~ 250 molecules per cell. UvrB and UvrD are also inducible by DNA damage. UvrC is not induced in the SOS response, however its homolog, Cho, is.
Enzymatic reaction of: Nucleotide excision repair (UvrABC Nucleotide Excision Repair Complex)
Synonyms: excinuclease, excision endonuclease, excision nuclease
EC Number: 3.1.25.-
The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.
The reaction is physiologically favored in the direction shown.
|Conserved-Region||16 -> 94|
|Conserved-Region||204 -> 239|
Peter D. Karp on Wed Jan 18, 2006:
Gene right-end position adjusted based on analysis performed in the 2005 E. coli annotation update [Riley06 ].
10/20/97 Gene b1913 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG11063; confirmed by SwissProt match.
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
Bugay14: Bugay AN, Krasavin EA, Parkhomenko AY, Vasilyeva MA (2014). "Modeling nucleotide excision repair and its impact on UV-induced mutagenesis during SOS-response in bacterial cells." J Theor Biol 364C;7-20. PMID: 25195002
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
Epshtein14: Epshtein V, Kamarthapu V, McGary K, Svetlov V, Ueberheide B, Proshkin S, Mironov A, Nudler E (2014). "UvrD facilitates DNA repair by pulling RNA polymerase backwards." Nature 505(7483);372-7. PMID: 24402227
Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938
Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394
Lin92: Lin JJ, Sancar A (1992). "Active site of (A)BC excinuclease. I. Evidence for 5' incision by UvrC through a catalytic site involving Asp399, Asp438, Asp466, and His538 residues." J Biol Chem 267(25);17688-92. PMID: 1387639
Moolenaar02: Moolenaar GF, van Rossum-Fikkert S, van Kesteren M, Goosen N (2002). "Cho, a second endonuclease involved in Escherichia coli nucleotide excision repair." Proc Natl Acad Sci U S A 99(3);1467-72. PMID: 11818552
Moolenaar87: Moolenaar GF, van Sluis CA, Backendorf C, van de Putte P (1987). "Regulation of the Escherichia coli excision repair gene uvrC. Overlap between the uvrC structural gene and the region coding for a 24 kD protein." Nucleic Acids Res 1987;15(10);4273-89. PMID: 3295776
Oh89: Oh EY, Claassen L, Thiagalingam S, Mazur S, Grossman L (1989). "ATPase activity of the UvrA and UvrAB protein complexes of the Escherichia coli UvrABC endonuclease." Nucleic Acids Res 17(11);4145-59. PMID: 2525700
Orren92: Orren DK, Selby CP, Hearst JE, Sancar A (1992). "Post-incision steps of nucleotide excision repair in Escherichia coli. Disassembly of the UvrBC-DNA complex by helicase II and DNA polymerase I." J Biol Chem 267(2);780-8. PMID: 1530937
Riley06: Riley M, Abe T, Arnaud MB, Berlyn MK, Blattner FR, Chaudhuri RR, Glasner JD, Horiuchi T, Keseler IM, Kosuge T, Mori H, Perna NT, Plunkett G, Rudd KE, Serres MH, Thomas GH, Thomson NR, Wishart D, Wanner BL (2006). "Escherichia coli K-12: a cooperatively developed annotation snapshot--2005." Nucleic Acids Res 34(1);1-9. PMID: 16397293
Verhoeven00: Verhoeven EE, van Kesteren M, Moolenaar GF, Visse R, Goosen N (2000). "Catalytic sites for 3' and 5' incision of Escherichia coli nucleotide excision repair are both located in UvrC." J Biol Chem 275(7);5120-3. PMID: 10671556
Verhoeven02: Verhoeven EE, Wyman C, Moolenaar GF, Goosen N (2002). "The presence of two UvrB subunits in the UvrAB complex ensures damage detection in both DNA strands." EMBO J 21(15);4196-205. PMID: 12145219
Wagner09: Wagner K, Moolenaar G, van Noort J, Goosen N (2009). "Single-molecule analysis reveals two separate DNA-binding domains in the Escherichia coli UvrA dimer." Nucleic Acids Res 37(6);1962-72. PMID: 19208636
Wang93: Wang J, Grossman L (1993). "Mutations in the helix-turn-helix motif of the Escherichia coli UvrA protein eliminate its specificity for UV-damaged DNA." J Biol Chem 268(7);5323-31. PMID: 8444906
MedinaRivera11: Medina-Rivera A, Abreu-Goodger C, Thomas-Chollier M, Salgado H, Collado-Vides J, van Helden J (2011). "Theoretical and empirical quality assessment of transcription factor-binding motifs." Nucleic Acids Res 39(3);808-24. PMID: 20923783
Vakulskas14: Vakulskas CA, Pannuri A, Cortes-Selva D, Zere TR, Ahmer BM, Babitzke P, Romeo T (2014). "Global effects of the DEAD-box RNA helicase DeaD (CsdA) on gene expression over a broad range of temperatures." Mol Microbiol 92(5);945-58. PMID: 24708042
vanSluis83: van Sluis CA, Moolenaar GF, Backendorf C (1983). "Regulation of the uvrC gene of Escherichia coli K12: localization and characterization of a damage-inducible promoter." EMBO J 1983;2(12);2313-8. PMID: 6321159
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