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Gene Review

oriC  - 

Escherichia coli O157:H7 str. EDL933

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Disease relevance of oriC


High impact information on oriC

  • Initiation is promoted by full methylation of GATC sites clustered in oriC; sequestration is specific to the hemimethylated forms generated by replication [5].
  • At a ratio of 10-20 monomers per oriC plasmid, the binding blocks initiation by preventing the opening of the 13-mer region by dnaA protein [6].
  • A particular outer membrane fraction previously defined as possessing specific affinity for the hemimethylated form of the origin of replication of the E. coli chromosome (oriC) is shown to inhibit the initiation of DNA synthesis at this site on hemimethylated DNA templates in vitro [7].
  • The E. coli cell surface specifically prevents the initiation of DNA replication at oriC on hemimethylated DNA templates [7].
  • The key inactivation step appears to be membrane inhibition of DnaA initiator protein binding to oriC [7].

Chemical compound and disease context of oriC


Biological context of oriC

  • Hda-deficient cells were very sensitive to variations in the cellular level of DnaA, and DnaA overproduction led to uncontrolled initiation of replication from oriC, causing severe growth retardation or cell death [13].
  • Our results suggest that the selection of the infrequent events of homologous recombination could be enhanced by the use of oriC plasmids derived from related mollicute species [1].
  • To examine whether methylation of the GATC sites present in the dnaA promoter region is responsible for the strict temporal coordination of initiation events at oriC as measured by the synchrony of initiation, we introduced point mutations eliminating three (TGW1) and five (TGW2) of the six GATC sites present in the dnaA promoter region [14].
  • In this study, oriC plasmids were evaluated in M. capricolum subsp. capricolum as genetic tools for (i) expression of heterologous proteins and (ii) gene inactivation by homologous recombination [1].
  • Loss of the integrated plasmid results in a temperature- and rich-medium-sensitive strain that replicates the chromosome from oriC and oriX [15].

Anatomical context of oriC

  • The binding of hemimethylated oriC to Escherichia coli membranes has been implicated in the prevention of premature reinitiation at newly replicated chromosomal origins in a reaction that involves the SeqA protein [16].
  • In the case of oriC plasmids, this inhibition was previously shown to be mediated by the specific affinity of the hemimethylated origin DNA for an outer cell membrane fraction [9].

Associations of oriC with chemical compounds

  • Similar periodic formation of the oriC complex was also observed when DNA elongation was inhibited by addition of nalidixic acid to the culture [17].
  • Guanine at position 3 determines DnaA-ATP preference, and changing this base to thymine at both I sites allows DnaA-ADP to bind and open oriC, although DNA strand separation is not precisely localized in the AT-rich region [18].
  • It is essentially the same as that described for the replication of oriC plasmid DNA [Fuller, R.S., Kaguni, J.M. & Kornberg, A. (1981) Proc. Natl. Acad. Sci. USA 78, 7370-7374] [19].
  • Cardiolipin binding of nucleotide-free dnaA protein prevents binding of ATP and initiation of oriC replication [20].
  • Because a region near the N terminus of DnaA is required for self-oligomerization and the loading of DnaB helicase at oriC, we asked if these functions are separable or interdependent by substituting many conserved amino acids in this region with alanine to identify essential residues [21].

Physical interactions of oriC


Other interactions of oriC


Analytical, diagnostic and therapeutic context of oriC


  1. Versatile use of oriC plasmids for functional genomics of Mycoplasma capricolum subsp. capricolum. Janis, C., Lartigue, C., Frey, J., Wróblewski, H., Thiaucourt, F., Blanchard, A., Sirand-Pugnet, P. Appl. Environ. Microbiol. (2005) [Pubmed]
  2. SeqA: a negative modulator of replication initiation in E. coli. Lu, M., Campbell, J.L., Boye, E., Kleckner, N. Cell (1994) [Pubmed]
  3. Protein HU in the enzymatic replication of the chromosomal origin of Escherichia coli. Dixon, N.E., Kornberg, A. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  4. Chromosomal replication origin from the marine bacterium Vibrio harveyi functions in Escherichia coli: oriC consensus sequence. Zyskind, J.W., Cleary, J.M., Brusilow, W.S., Harding, N.E., Smith, D.W. Proc. Natl. Acad. Sci. U.S.A. (1983) [Pubmed]
  5. E. coli SeqA protein binds oriC in two different methyl-modulated reactions appropriate to its roles in DNA replication initiation and origin sequestration. Slater, S., Wold, S., Lu, M., Boye, E., Skarstad, K., Kleckner, N. Cell (1995) [Pubmed]
  6. A novel protein binds a key origin sequence to block replication of an E. coli minichromosome. Hwang, D.S., Kornberg, A. Cell (1990) [Pubmed]
  7. The E. coli cell surface specifically prevents the initiation of DNA replication at oriC on hemimethylated DNA templates. Landoulsi, A., Malki, A., Kern, R., Kohiyama, M., Hughes, P. Cell (1990) [Pubmed]
  8. Insertion of an R1 plasmid into the origin of replication of the E. coli chromosome: random timing of replication of the hybrid chromosome. Koppes, L., Nordström, K. Cell (1986) [Pubmed]
  9. Inhibition of DNA synthesis at the hemimethylated pBR322 origin of replication by a cell membrane fraction. Malki, A., Kern, R., Kohiyama, M., Hughes, P. Nucleic Acids Res. (1992) [Pubmed]
  10. Acidic phospholipids inhibit the DNA-binding activity of DnaA protein, the initiator of chromosomal DNA replication in Escherichia coli. Makise, M., Mima, S., Katsu, T., Tsuchiya, T., Mizushima, T. Mol. Microbiol. (2002) [Pubmed]
  11. Biological characterization of cyclothialidine, a new DNA gyrase inhibitor. Nakada, N., Shimada, H., Hirata, T., Aoki, Y., Kamiyama, T., Watanabe, J., Arisawa, M. Antimicrob. Agents Chemother. (1993) [Pubmed]
  12. The central lysine in the P-loop motif of the Escherichia coli DnaA protein is essential for initiating DNA replication from the chromosomal origin, oriC, and the F factor origin, oriS, but is dispensable for initiation from the P1 plasmid origin, oriR. Skovgaard, O., Olesen, K., Wright, A. Plasmid (1998) [Pubmed]
  13. Hda-mediated inactivation of the DnaA protein and dnaA gene autoregulation act in concert to ensure homeostatic maintenance of the Escherichia coli chromosome. Riber, L., Olsson, J.A., Jensen, R.B., Skovgaard, O., Dasgupta, S., Marinus, M.G., Løbner-Olesen, A. Genes Dev. (2006) [Pubmed]
  14. The synchrony phenotype persists after elimination of multiple GATC sites from the dnaA promoter of Escherichia coli. Wilkinson, T.G., Kedar, G.C., Lee, C., Guzmán, E.C., Smith, D.W., Zyskind, J.W. J. Bacteriol. (2006) [Pubmed]
  15. oriX: a new replication origin in E. coli. de Massy, B., Patte, J., Louarn, J.M., Bouché, J.P. Cell (1984) [Pubmed]
  16. High-affinity binding of hemimethylated oriC by Escherichia coli membranes is mediated by a multiprotein system that includes SeqA and a newly identified factor, SeqB. Shakibai, N., Ishidate, K., Reshetnyak, E., Gunji, S., Kohiyama, M., Rothfield, L. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  17. Periodic formation of the oriC complex of Escherichia coli. Gayama, S., Kataoka, T., Wachi, M., Tamura, G., Nagai, K. EMBO J. (1990) [Pubmed]
  18. Two discriminatory binding sites in the Escherichia coli replication origin are required for DNA strand opening by initiator DnaA-ATP. McGarry, K.C., Ryan, V.T., Grimwade, J.E., Leonard, A.C. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  19. Replication of mini-P1 plasmid DNA in vitro requires two initiation proteins, encoded by the repA gene of phage P1 and the dnaA gene of Escherichia coli. Wickner, S.H., Chattoraj, D.K. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  20. Cardiolipin activation of dnaA protein, the initiation protein of replication in Escherichia coli. Sekimizu, K., Kornberg, A. J. Biol. Chem. (1988) [Pubmed]
  21. An essential tryptophan of Escherichia coli DnaA protein functions in oligomerization at the E. coli replication origin. Felczak, M.M., Simmons, L.A., Kaguni, J.M. J. Biol. Chem. (2005) [Pubmed]
  22. Hemi-methylated oriC DNA binding activity found in non-specific acid phosphatase. Reshetnyak, E., d'Alençon, E., Kern, R., Taghbalout, A., Guillaud, P., Kohiyama, M. Mol. Microbiol. (1999) [Pubmed]
  23. A novel role for cAMP in the control of the activity of the E. coli chromosome replication initiator protein, DnaA. Hughes, P., Landoulsi, A., Kohiyama, M. Cell (1988) [Pubmed]
  24. Dysfunctional MreB inhibits chromosome segregation in Escherichia coli. Kruse, T., Møller-Jensen, J., Løbner-Olesen, A., Gerdes, K. EMBO J. (2003) [Pubmed]
  25. Cloning and expression of the Escherichia coli replication origin in a single-stranded DNA phage. Kaguni, J., LaVerne, L.S., Ray, D.S. Proc. Natl. Acad. Sci. U.S.A. (1979) [Pubmed]
  26. Replication cycle dependent association of SeqA to the outer membrane fraction of E. coli. d'Alençon, E., Taghbalout, A., Kern, R., Kohiyama, M. Biochimie (1999) [Pubmed]
  27. Rat DNA polymerase beta substitutes the repairing activity of DNA polymerase I in the lethal effect of UV light. Hern??ndez-Escamilla, R., Espinosa-Lara, J.M., Quintana-Hau, J.D., Uribe-Luna, S., Loyola-Abitia, P., Santiago-Hern??ndez, J.C., Maldonado-Rodr??guez, R. Rev. Latinoam. Microbiol. (2002) [Pubmed]
  28. Enzymatic replication of E. coli chromosomal origin is bidirectional. Kaguni, J.M., Fuller, R.S., Kornberg, A. Nature (1982) [Pubmed]
  29. Mechanism of origin unwinding: sequential binding of DnaA to double- and single-stranded DNA. Speck, C., Messer, W. EMBO J. (2001) [Pubmed]
  30. The chromosome origin of Escherichia coli stabilizes DnaA protein during rejuvenation by phospholipids. Crooke, E., Castuma, C.E., Kornberg, A. J. Biol. Chem. (1992) [Pubmed]
  31. The sequence requirements for a functional Escherichia coli replication origin are different for the chromosome and a minichromosome. Weigel, C., Messer, W., Preiss, S., Welzeck, M., Morigen, n.u.l.l., Boye, E. Mol. Microbiol. (2001) [Pubmed]
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