Gene Symbol: dksA
Description: transcriptional regulator of rRNA transcription; DnaK suppressor protein
Alias: ECK0144, JW0141, msmA
Species: Escherichia coli str. K-12 substr. MG1655

Top Publications

  1. Paul B, Berkmen M, Gourse R. DksA potentiates direct activation of amino acid promoters by ppGpp. Proc Natl Acad Sci U S A. 2005;102:7823-8 pubmed
    ..Recently, we showed that DksA binds to RNA polymerase and greatly enhances direct effects of ppGpp on the negative control of rRNA promoters...
  2. Yamanaka K, Mitani T, Ogura T, Niki H, Hiraga S. Cloning, sequencing, and characterization of multicopy suppressors of a mukB mutation in Escherichia coli. Mol Microbiol. 1994;13:301-12 pubmed
    ..To identify proteins interacting with the MukB protein, we isolated three multicopy suppressors (msmA, msmB, and msmC) to the temperature-sensitive colony formation of the mukB106 mutation...
  3. Magnusson L, Gummesson B, Joksimović P, Farewell A, Nystrom T. Identical, independent, and opposing roles of ppGpp and DksA in Escherichia coli. J Bacteriol. 2007;189:5193-202 pubmed
    The recent discovery that the protein DksA acts as a coregulator of genes controlled by ppGpp led us to investigate the similarities and differences between the relaxed phenotype of a ppGpp-deficient mutant and the phenotype of a strain ..
  4. Costanzo A, Nicoloff H, Barchinger S, Banta A, Gourse R, Ades S. ppGpp and DksA likely regulate the activity of the extracytoplasmic stress factor sigmaE in Escherichia coli by both direct and indirect mechanisms. Mol Microbiol. 2008;67:619-32 pubmed
    ..In vivo experiments with sigmaE are consistent with this model. However, ppGpp and its cofactor DksA can also activate transcription by EsigmaEin vitro, suggesting that the effects of ppGpp on sigmaE activity are ..
  5. Gralla J. Escherichia coli ribosomal RNA transcription: regulatory roles for ppGpp, NTPs, architectural proteins and a polymerase-binding protein. Mol Microbiol. 2005;55:973-7 pubmed
    ..This review discusses the current state of affairs, including recent information about the involvement of two nucleotide regulators, two architectural protein regulators, one new co-regulator and stalled ribosomes. ..
  6. Paul B, Ross W, Gaal T, Gourse R. rRNA transcription in Escherichia coli. Annu Rev Genet. 2004;38:749-70 pubmed
    ..of rRNA transcription initiation; and (c) identification of a new component of the transcription machinery, DksA, that is absolutely required for regulation of rRNA promoter activity...
  7. Perederina A, Svetlov V, Vassylyeva M, Tahirov T, Yokoyama S, Artsimovitch I, et al. Regulation through the secondary channel--structural framework for ppGpp-DksA synergism during transcription. Cell. 2004;118:297-309 pubmed
    ..We show that the DksA protein is a crucial component of ppGpp-dependent regulation. The 2...
  8. Kang P, Craig E. Identification and characterization of a new Escherichia coli gene that is a dosage-dependent suppressor of a dnaK deletion mutation. J Bacteriol. 1990;172:2055-64 pubmed
    ..The dnaK suppressor gene, designated dksA, maps near the mrcB gene (3.7 min on the E. coli chromosome)...
  9. Meddows T, Savory A, Grove J, Moore T, Lloyd R. RecN protein and transcription factor DksA combine to promote faithful recombinational repair of DNA double-strand breaks. Mol Microbiol. 2005;57:97-110 pubmed
    ..When breaks are induced at a single site, the SOS-inducible RecN protein and the transcription factor DksA combine to promote efficient repair...

More Information


  1. Magnusson L, Farewell A, Nystrom T. ppGpp: a global regulator in Escherichia coli. Trends Microbiol. 2005;13:236-42 pubmed
    ..In addition, new insights into the mechanism by which ppGpp affects gene expression have been achieved owing to in vitro studies of ppGpp function, complemented by structural studies of the ppGpp-RNA polymerase complex. ..
  2. Brown L, Gentry D, Elliott T, Cashel M. DksA affects ppGpp induction of RpoS at a translational level. J Bacteriol. 2002;184:4455-65 pubmed
    ..b>DksA is found to affect RpoS abundance in a manner related to ppGpp. Deleting dksA blocks rpoS induction by ppGpp...
  3. Rutherford S, Lemke J, Vrentas C, Gaal T, Ross W, Gourse R. Effects of DksA, GreA, and GreB on transcription initiation: insights into the mechanisms of factors that bind in the secondary channel of RNA polymerase. J Mol Biol. 2007;366:1243-57 pubmed
    Escherichia coli DksA, GreA, and GreB have similar structures and bind to the same location on RNA polymerase (RNAP), the secondary channel...
  4. Aberg A, Shingler V, Balsalobre C. Regulation of the fimB promoter: a case of differential regulation by ppGpp and DksA in vivo. Mol Microbiol. 2008;67:1223-41 pubmed publisher
    ..we show that in contrast to the previously described decreased fimbriation observed in a ppGpp-deficient strain, DksA deficiency results in a hyperfimbriated state...
  5. Paul B, Barker M, Ross W, Schneider D, Webb C, Foster J, et al. DksA: a critical component of the transcription initiation machinery that potentiates the regulation of rRNA promoters by ppGpp and the initiating NTP. Cell. 2004;118:311-22 pubmed
    ..We show here that DksA, a protein previously unsuspected as a transcription factor, is absolutely required for rRNA regulation...
  6. Potrykus K, Vinella D, Murphy H, Szalewska Palasz A, D Ari R, Cashel M. Antagonistic regulation of Escherichia coli ribosomal RNA rrnB P1 promoter activity by GreA and DksA. J Biol Chem. 2006;281:15238-48 pubmed
    The Escherichia coli proteins DksA, GreA, and GreB are all structural homologs that bind the secondary channel of RNA polymerase (RNAP) but are thought to act at different levels of transcription...
  7. Doran T, Loh S, Firth N, Skurray R. Molecular analysis of the F plasmid traVR region: traV encodes a lipoprotein. J Bacteriol. 1994;176:4182-6 pubmed
    ..The deduced product of traR was found to share amino acid similarity with proteins from the bacteriophages 186 and P2 and with the dosage-dependent dnaK suppressor DksA.
  8. Nakanishi N, Abe H, Ogura Y, Hayashi T, Tashiro K, Kuhara S, et al. ppGpp with DksA controls gene expression in the locus of enterocyte effacement (LEE) pathogenicity island of enterohaemorrhagic Escherichia coli through activation of two virulence regulatory genes. Mol Microbiol. 2006;61:194-205 pubmed publisher
    ..activation was dependent on relA and spoT, which encode enzymes for the synthesis and degradation of ppGpp, and on dksA, which encodes an RNA polymerase accessory protein required for the stringent response...
  9. Potrykus K, Cashel M. (p)ppGpp: still magical?. Annu Rev Microbiol. 2008;62:35-51 pubmed publisher
    ..Many basic questions still exist. This review tries to focus on some issues that linger even for the most widely characterized bacterial strains. ..
  10. Doniselli N, Rodriguez Aliaga P, Amidani D, Bardales J, Bustamante C, Guerra D, et al. New insights into the regulatory mechanisms of ppGpp and DksA on Escherichia coli RNA polymerase-promoter complex. Nucleic Acids Res. 2015;43:5249-62 pubmed publisher
    The stringent response modulators, guanosine tetraphosphate (ppGpp) and protein DksA, bind RNA polymerase (RNAP) and regulate gene expression to adapt bacteria to different environmental conditions...
  11. Hirsch M, Elliott T. Role of ppGpp in rpoS stationary-phase regulation in Escherichia coli. J Bacteriol. 2002;184:5077-87 pubmed
    ..A number of other genes that have been suggested as regulators of rpoS were tested, including dksA, dsrA, barA, ppkx, and hfq...
  12. Hansen S, Lewis K, Vulic M. Role of global regulators and nucleotide metabolism in antibiotic tolerance in Escherichia coli. Antimicrob Agents Chemother. 2008;52:2718-26 pubmed publisher
    ..surA (peptidyl-prolyl cis-trans isomerase), fis and hns (global regulators), hnr (response regulator of RpoS), dksA (transcriptional regulator of rRNA transcription), ygfA (5-formyl-tetrahydrofolate cyclo-ligase), and yigB (flavin ..
  13. Satory D, Gordon A, Wang M, Halliday J, Golding I, Herman C. DksA involvement in transcription fidelity buffers stochastic epigenetic change. Nucleic Acids Res. 2015;43:10190-9 pubmed publisher
    b>DksA is an auxiliary transcription factor that interacts with RNA polymerase and influences gene expression. Depending on the promoter, DksA can be a positive or negative regulator of transcription initiation...
  14. Bass S, Gu Q, Christen A. Multicopy suppressors of prc mutant Escherichia coli include two HtrA (DegP) protease homologs (HhoAB), DksA, and a truncated R1pA. J Bacteriol. 1996;178:1154-61 pubmed
    ..A second multicopy prc suppressor is the dksA (dnaK suppressor) gene, which is also a multicopy suppressor of defects in the heat shock genes dnaK, dnaJ, and ..
  15. Stallings C, Glickman M. CarD: a new RNA polymerase modulator in mycobacteria. Transcription. 2011;2:15-8 pubmed publisher
    ..This article will review our present state of knowledge regarding CarD and compare the known functions of CarD with other RNAP binding proteins in E. coli, emphasizing how this information can guide future investigations. ..
  16. Gopalkrishnan S, Nicoloff H, Ades S. Co-ordinated regulation of the extracytoplasmic stress factor, sigmaE, with other Escherichia coli sigma factors by (p)ppGpp and DksA may be achieved by specific regulation of individual holoenzymes. Mol Microbiol. 2014;93:479-93 pubmed publisher
    ..The DksA protein often potentiates the effects of (p)ppGpp...
  17. Ishii Y, Yamada H, Yamashino T, Ohashi K, Katoh E, Shindo H, et al. Deletion of the yhhP gene results in filamentous cell morphology in Escherichia coli. Biosci Biotechnol Biochem. 2000;64:799-807 pubmed
    ..Another multicopy suppressor gene was identified as the dksA gene...
  18. Ohkubo S, Yamaguchi K. A suppressor of mutations in the region adjacent to iterons of pSC101 ori. J Bacteriol. 1997;179:2089-91 pubmed
    ..The nucleotide sequence of the suppressor revealed that the suppressor gene was identical to dksA, which encodes a multicopy suppressor of the heat shock gene dnaK.
  19. Kirkpatrick C, Maurer L, Oyelakin N, Yoncheva Y, Maurer R, Slonczewski J. Acetate and formate stress: opposite responses in the proteome of Escherichia coli. J Bacteriol. 2001;183:6466-77 pubmed
  20. Parshin A, Shiver A, Lee J, Ozerova M, Schneidman Duhovny D, Gross C, et al. DksA regulates RNA polymerase in Escherichia coli through a network of interactions in the secondary channel that includes Sequence Insertion 1. Proc Natl Acad Sci U S A. 2015;112:E6862-71 pubmed publisher
    ..response to amino acid starvation is orchestrated by guanosine-3',5'-bisdiphosphate and the transcription factor DksA. DksA alters transcription by binding to RNA polymerase and allosterically modulating its activity...
  21. Bernardo L, Johansson L, Solera D, Skarfstad E, Shingler V. The guanosine tetraphosphate (ppGpp) alarmone, DksA and promoter affinity for RNA polymerase in regulation of sigma-dependent transcription. Mol Microbiol. 2006;60:749-64 pubmed
    The RNA polymerase-binding protein DksA is a cofactor required for guanosine tetraphosphate (ppGpp)-responsive control of transcription from sigma70 promoters...
  22. Kawamukai M, Utsumi R, Takeda K, Higashi A, Matsuda H, Choi Y, et al. Nucleotide sequence and characterization of the sfs1 gene: sfs1 is involved in CRP*-dependent mal gene expression in Escherichia coli. J Bacteriol. 1991;173:2644-8 pubmed
    ..Overexpression of the sfs1 gene in MK2001 resulted in a 10-fold increase of amylomaltase, which was still dependent on MalT. These results suggest that Sfs1 could be a new regulatory factor involved in maltose metabolism. ..
  23. Aberg A, Fernández Vázquez J, Cabrer Panes J, Sanchez A, Balsalobre C. Similar and divergent effects of ppGpp and DksA deficiencies on transcription in Escherichia coli. J Bacteriol. 2009;191:3226-36 pubmed publisher
    The concerted action of ppGpp and DksA in transcription has been widely documented...
  24. Furman R, Tsodikov O, Wolf Y, Artsimovitch I. An insertion in the catalytic trigger loop gates the secondary channel of RNA polymerase. J Mol Biol. 2013;425:82-93 pubmed publisher
    Escherichia coli DksA and GreB bind to RNA polymerase (RNAP), reaching inside the secondary channel, with similar affinities but have different cellular functions...
  25. Mallik P, Paul B, Rutherford S, Gourse R, Osuna R. DksA is required for growth phase-dependent regulation, growth rate-dependent control, and stringent control of fis expression in Escherichia coli. J Bacteriol. 2006;188:5775-82 pubmed
    b>DksA is a critical transcription factor in Escherichia coli that binds to RNA polymerase and potentiates control of rRNA promoters and certain amino acid promoters...
  26. Wu J, Xie J. Magic spot: (p) ppGpp. J Cell Physiol. 2009;220:297-302 pubmed publisher
    ..Therefore, more attention should be focused on the molecular mechanisms of (p) ppGpp, as it is the foundation to understanding how bacteria adapt to extreme circumstances through the stringent response. ..
  27. Haugen S, Berkmen M, Ross W, Gaal T, Ward C, Gourse R. rRNA promoter regulation by nonoptimal binding of sigma region 1.2: an additional recognition element for RNA polymerase. Cell. 2006;125:1069-82 pubmed
    ..2-discriminator interaction, rRNA promoters create the short-lived complex required for specific responses to the RNAP binding factors ppGpp and DksA, ultimately accounting for regulation of ribosome synthesis.
  28. Lemke J, Sanchez Vazquez P, Burgos H, Hedberg G, Ross W, Gourse R. Direct regulation of Escherichia coli ribosomal protein promoters by the transcription factors ppGpp and DksA. Proc Natl Acad Sci U S A. 2011;108:5712-7 pubmed publisher
    ..protein operons are regulated directly by two transcription factors, the small RNA polymerase-binding protein DksA and the nutritional stress-induced nucleotide ppGpp...
  29. Roberts J. Promoter-specific control of E. coli RNA polymerase by ppGpp and a general transcription factor. Genes Dev. 2009;23:143-6 pubmed publisher
    ..A small protein, DksA, which binds in the secondary channel of RNA polymerase, possibly along with other general regulatory factors, ..
  30. Satory D, Halliday J, Sivaramakrishnan P, Lua R, Herman C. Characterization of a novel RNA polymerase mutant that alters DksA activity. J Bacteriol. 2013;195:4187-94 pubmed publisher
    The auxiliary factor DksA is a global transcription regulator and, with the help of ppGpp, controls the nutritional stress response in Escherichia coli...
  31. Kolmsee T, Delic D, Agyenim T, Calles C, Wagner R. Differential stringent control of Escherichia coli rRNA promoters: effects of ppGpp, DksA and the initiating nucleotides. Microbiology. 2011;157:2871-9 pubmed publisher
    ..The presence of DksA was shown to be crucial for the ppGpp-dependent downregulation of all P1 promoters...
  32. Chandrangsu P, Lemke J, Gourse R. The dksA promoter is negatively feedback regulated by DksA and ppGpp. Mol Microbiol. 2011;80:1337-48 pubmed publisher
    Escherichia coli DksA is an RNA polymerase (RNAP)-binding protein required for the regulation of a number of promoters, including those for the biosynthesis of rRNA, many ribosomal proteins, components of the flagellum, and several amino ..
  33. Sharma A, Payne S. Induction of expression of hfq by DksA is essential for Shigella flexneri virulence. Mol Microbiol. 2006;62:469-79 pubmed
    ..Studies with Shigella flexneri show that hfq transcription is regulated by a pleiotropic regulator, DksA. Comparison of gene expression profiles of wild type and dksA mutant S...
  34. Blankschien M, Potrykus K, Grace E, Choudhary A, Vinella D, Cashel M, et al. TraR, a homolog of a RNAP secondary channel interactor, modulates transcription. PLoS Genet. 2009;5:e1000345 pubmed publisher
    ..Specifically, the small nucleotide ppGpp, along with DksA, a RNAP secondary channel interacting factor, modifies the kinetics of transcription initiation, resulting in, ..
  35. Lemke J, Durfee T, Gourse R. DksA and ppGpp directly regulate transcription of the Escherichia coli flagellar cascade. Mol Microbiol. 2009;74:1368-79 pubmed publisher
    ..studies have reported that flagellar transcription is altered in cells lacking the transcription regulators DksA or ppGpp, but some or all reported effects could be indirect, and some are contradictory...
  36. Chandrangsu P, Wang L, Choi S, Gourse R. Suppression of a dnaKJ deletion by multicopy dksA results from non-feedback-regulated transcripts that originate upstream of the major dksA promoter. J Bacteriol. 2012;194:1437-46 pubmed publisher
    b>DksA is an RNA polymerase (RNAP) binding transcription factor that controls expression of a large number of genes in concert with the small-molecule "alarmone" ppGpp...
  37. Suthers P, Gourse R, Yin J. Rapid responses of ribosomal RNA synthesis to nutrient shifts. Biotechnol Bioeng. 2007;97:1230-45 pubmed
    ..have identified regulatory roles for guanosine tetraphosphate (ppGpp), the initiating nucleotide, and the protein DksA. To what extent findings from in vitro studies can be used to quantitatively predict in vivo responses to changing ..
  38. Dubois D, Blaise M, Becker H, Campanacci V, Keith G, Giege R, et al. An aminoacyl-tRNA synthetase-like protein encoded by the Escherichia coli yadB gene glutamylates specifically tRNAAsp. Proc Natl Acad Sci U S A. 2004;101:7530-5 pubmed
    ..The yadB gene is expressed in wild-type E. coli as an operon with the dksA gene, which encodes a protein involved in the general stress response by means of its action at the translational ..
  39. Blankschien M, Lee J, Grace E, Lennon C, Halliday J, Ross W, et al. Super DksAs: substitutions in DksA enhancing its effects on transcription initiation. EMBO J. 2009;28:1720-31 pubmed publisher
    At specific times during bacterial growth, the transcription factor DksA and the unusual nucleotide regulator ppGpp work synergistically to inhibit some Escherichia coli promoters (e.g. rRNA promoters) and to stimulate others (e.g...
  40. Liberek K, Galitski T, Zylicz M, Georgopoulos C. The DnaK chaperone modulates the heat shock response of Escherichia coli by binding to the sigma 32 transcription factor. Proc Natl Acad Sci U S A. 1992;89:3516-20 pubmed
    ..Consistent with the fact that dnaK756 mutant bacteria overexpress heat shock proteins at all temperatures, purified DnaK756 mutant protein did not appreciably bind to sigma 32. ..
  41. Potenza L, Ubaldi L, De Sanctis R, De Bellis R, Cucchiarini L, Dachà M. Effects of a static magnetic field on cell growth and gene expression in Escherichia coli. Mutat Res. 2004;561:53-62 pubmed
    ..One clone, expressed only in the exposed cells, corresponds to a putative transposase. This is of particular interest in that it suggests that exposure to a magnetic field may stimulate transposition activity. ..
  42. Srivatsan A, Wang J. Control of bacterial transcription, translation and replication by (p)ppGpp. Curr Opin Microbiol. 2008;11:100-5 pubmed publisher
    ..p)ppGpp, along with the transcription factor DksA, has profound effects on transcription initiation in E. coli...
  43. Rutherford S, Villers C, Lee J, Ross W, Gourse R. Allosteric control of Escherichia coli rRNA promoter complexes by DksA. Genes Dev. 2009;23:236-48 pubmed publisher
    The Escherichia coli DksA protein inserts into the RNA polymerase (RNAP) secondary channel, modifying the transcription initiation complex so that promoters with specific kinetic characteristics are regulated by changes in the ..
  44. Szalewska Palasz A, Johansson L, Bernardo L, Skarfstad E, Stec E, Brannstrom K, et al. Properties of RNA polymerase bypass mutants: implications for the role of ppGpp and its co-factor DksA in controlling transcription dependent on sigma54. J Biol Chem. 2007;282:18046-56 pubmed
    The bacterial nutritional and stress alarmone ppGpp and its co-factor DksA directly bind RNA polymerase to regulate its activity at certain sigma70-dependent promoters...
  45. Lee J, Lennon C, Ross W, Gourse R. Role of the coiled-coil tip of Escherichia coli DksA in promoter control. J Mol Biol. 2012;416:503-17 pubmed publisher
    Escherichia coli DksA works in conjunction with the small-molecule ppGpp to regulate transcription initiation negatively or positively, depending on the identity of the promoter...
  46. Salem A, Nakano T, Takuwa M, Matoba N, Tsuboi T, Terato H, et al. Genetic analysis of repair and damage tolerance mechanisms for DNA-protein cross-links in Escherichia coli. J Bacteriol. 2009;191:5657-68 pubmed publisher
    ..and NER, the mutation of genes involved in several aspects of DNA repair and transactions, such as recQ, xth nfo, dksA, and topA, rendered cells slightly but significantly sensitive to FA but not azaC, possibly reflecting the ..
  47. Lennon C, Ross W, Martin Tumasz S, Toulokhonov I, Vrentas C, Rutherford S, et al. Direct interactions between the coiled-coil tip of DksA and the trigger loop of RNA polymerase mediate transcriptional regulation. Genes Dev. 2012;26:2634-46 pubmed publisher
    Escherichia coli DksA is a transcription factor that binds to RNA polymerase (RNAP) without binding to DNA, destabilizing RNAP-promoter interactions, sensitizing RNAP to the global regulator ppGpp, and regulating transcription of several ..
  48. Hardy C, Cozzarelli N. A genetic selection for supercoiling mutants of Escherichia coli reveals proteins implicated in chromosome structure. Mol Microbiol. 2005;57:1636-52 pubmed
    ..Three of these proteins: H-NS, Fis and DksA, have clear ties to chromosome biology...
  49. Ross W, Sanchez Vazquez P, Chen A, Lee J, Burgos H, Gourse R. ppGpp Binding to a Site at the RNAP-DksA Interface Accounts for Its Dramatic Effects on Transcription Initiation during the Stringent Response. Mol Cell. 2016;62:811-823 pubmed publisher
    ..characterized previously (site 1) and a second identified here at an interface of RNAP and the transcription factor DksA (site 2)...
  50. Vassylyeva M, Perederina A, Svetlov V, Yokoyama S, Artsimovitch I, Vassylyev D. Cloning, expression, purification, crystallization and initial crystallographic analysis of transcription factor DksA from Escherichia coli. Acta Crystallogr D Biol Crystallogr. 2004;60:1611-3 pubmed
    The Escherichia coli gene encoding a regulator of stringent response and virulence, DksA, which contains a canonical Zn finger motif, was cloned and expressed, and the purified protein was crystallized by the hanging-drop vapor-diffusion ..
  51. Lennon C, Gaal T, Ross W, Gourse R. Escherichia coli DksA binds to Free RNA polymerase with higher affinity than to RNA polymerase in an open complex. J Bacteriol. 2009;191:5854-8 pubmed publisher
    The transcription factor DksA binds in the secondary channel of RNA polymerase (RNAP) and alters transcriptional output without interacting with DNA...
  52. Vrentas C, Gaal T, Ross W, Ebright R, Gourse R. Response of RNA polymerase to ppGpp: requirement for the omega subunit and relief of this requirement by DksA. Genes Dev. 2005;19:2378-87 pubmed
    ..b>DksA, a transcription factor that works in concert with ppGpp to regulate rRNA expression in vivo and in vitro, fully ..
  53. Merrikh H, Ferrazzoli A, Lovett S. Growth phase and (p)ppGpp control of IraD, a regulator of RpoS stability, in Escherichia coli. J Bacteriol. 2009;191:7436-46 pubmed publisher
    ..Surprisingly, DksA, normally required for transcriptional effects of the stringent response, repressed iraD expression, suggesting ..
  54. Webb C, Moreno M, Wilmes Riesenberg M, Curtiss R, Foster J. Effects of DksA and ClpP protease on sigma S production and virulence in Salmonella typhimurium. Mol Microbiol. 1999;34:112-23 pubmed
    ..The second is dksA, encoding a protein of unknown function not previously associated with regulating sigmaS levels...