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Regulation of the replication cycle: conserved and diverse regulatory systems for DnaA and oriC

Nature Reviews Microbiology volume 8, pages 163–170 (2010)Cite this article

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Abstract

Chromosomal replication must be limited to once and only once per cell cycle. This is accomplished by multiple regulatory pathways that govern initiator proteins and replication origins. A principal feature of DNA replication is the coupling of the replication reaction to negative-feedback regulation. Some of the factors that are important in this process have been discovered, including the clamp (DNA polymerase III subunit-β (DnaN)), the datA locus, SeqA, DnaA homologue protein (Hda) and YabA, as well as factors that are involved at other stages of the regulatory mechanism, such as DnaA initiator-associating protein (DiaA), the DnaA-reactivating sequence (DARS) loci and Soj. Here, we describe the regulation of DnaA, one of the central proteins involved in bacterial DNA replication, by these factors in Escherichia coli, Bacillus subtilis and Caulobacter crescentus.

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Figure 1: Regulatory systems for replication initiation in bacteria and eukaryotes.
Figure 2: Model mechanism of initiation at the origin of replication in Escherichia coli.
Figure 3: Tertiary structures of Escherichia coli DnaA domains.
Figure 4: Regulatory systems for chromosomal replication initiation.
Figure 5: Replication initiation and regulatory inactivation of DnaA (RIDA) in Escherichia coli.

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References

  1. Messer, W. The bacterial replication initiator DnaA. DnaA and oriC, the bacterial mode to initiate DNA replication. FEMS Microbiol. Rev. 26, 355–374 (2002).

    CAS  PubMed  Google Scholar 

  2. Mott, M. L. & Berger, J. M. DNA replication initiation: mechanisms and regulation in bacteria. Nature Rev. Microbiol. 5, 343–354 (2007).

    Article  CAS  Google Scholar 

  3. Ozaki, S. & Katayama, T. DnaA structure, function, and dynamics in the initiation at the chromosomal origin. Plasmid 62, 71–82 (2009).

    Article  CAS  PubMed  Google Scholar 

  4. Nishitani, H. & Lygerou, Z. Control of DNA replication licensing in a cell cycle. Genes Cells 7, 523–534 (2002).

    Article  CAS  PubMed  Google Scholar 

  5. Bell, S. P. & Dutta, A. DNA replication in eukaryotic cells. Annu. Rev. Biochem. 71, 333–374 (2002).

    Article  CAS  PubMed  Google Scholar 

  6. Kornberg, A. & Baker, T. A. DNA Replication 2nd edn (Freeman and Co., New York, 1992).

    Google Scholar 

  7. O'Donnell, M. Replisome architecture and dynamics in Escherichia coli. J. Biol. Chem. 281, 10653–10656 (2006).

    Article  CAS  PubMed  Google Scholar 

  8. Georgescu, R. E. et al. Structure of a sliding clamp on DNA. Cell 132, 43–54 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Katayama, T. Feedback controls restrain the initiation of Escherichia coli chromosomal replication. Mol. Microbiol. 41, 9–17 (2001).

    Article  CAS  PubMed  Google Scholar 

  10. Zegerman, P. & Diffley, J. F. Phosphorylation of Sld2 and Sld3 by cyclin-dependent kinases promotes DNA replication in budding yeast. Nature 445, 281–285 (2007).

    Article  CAS  PubMed  Google Scholar 

  11. Tanaka, S. et al. CDK-dependent phosphorylation of Sld2 and Sld3 initiates DNA replication in budding yeast. Nature 445, 328–332 (2007).

    Article  CAS  PubMed  Google Scholar 

  12. Nguyen, V. Q., Co, C. & Li, J. J. Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms. Nature 411, 1068–1073 (2001).

    Article  CAS  PubMed  Google Scholar 

  13. Weinreich, M., Liang, C., Chen, H. H. & Stillman, B. Binding of cyclin-dependent kinases to ORC and Cdc6p regulates the chromosome replication cycle. Proc. Natl Acad. Sci. USA 98, 11211–11217 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kurokawa, K., Nishida, S., Emoto, A., Sekimizu, K. & Katayama, T. Replication cycle-coordinated change of the adenine nucleotide-bound forms of DnaA protein in Escherichia coli. EMBO J. 18, 6642–6652 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Roth, A., Urmoneit, B. & Messer, W. Functions of histone-like proteins in the initiation of DNA replication at oriC of Escherichia coli. Biochimie 76, 917–923 (1994).

    Article  CAS  PubMed  Google Scholar 

  16. Ishida, T. et al. DiaA, a novel DnaA-binding protein, ensures the timely initiation of Escherichia coli chromosome replication. J. Biol. Chem. 279, 45546–45555 (2004).

    Article  CAS  PubMed  Google Scholar 

  17. Keyamura, K. et al. The interaction of DiaA and DnaA regulates the replication cycle in E. coli by directly promoting ATP DnaA-specific initiation complexes. Genes Dev. 21, 2083–2099 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Erzberger, J. P., Mott, M. L. & Berger, J. M. Structural basis for ATP-dependent DnaA assembly and replication-origin remodeling. Nature Struct. Mol. Biol. 13, 676–683 (2006).

    Article  CAS  Google Scholar 

  19. Ozaki, S. et al. A common mechanism for the ATP-DnaA-dependent formation of open complexes at the replication origin. J. Biol. Chem. 283, 8351–8362 (2008).

    Article  CAS  PubMed  Google Scholar 

  20. McGarry, K. C., Ryan, V. T., Grimwade, J. E. & Leonard, A. C. Two discriminatory binding sites in the Escherichia coli replication origin are required for DNA strand opening by initiator DnaA-ATP. Proc. Natl Acad. Sci. USA 101, 2811–2816 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kawakami, H., Keyamura, K. & Katayama, T. Formation of an ATP-DnaA-specific initiation complex requires DnaA Arginine 285, a conserved motif in the AAA+ protein family. J. Biol. Chem. 280, 27420–27430 (2005).

    Article  CAS  PubMed  Google Scholar 

  22. Ryan, V. T., Grimwade, J. E., Nievera, C. J. & Leonard, A. C. IHF and HU stimulate assembly of pre-replication complexes at Escherichia coli oriC by two different mechanisms. Mol. Microbiol. 46, 113–124 (2002).

    Article  CAS  PubMed  Google Scholar 

  23. Swinger, K. K. & Rice, P. A. IHF and HU: flexible architects of bent DNA. Curr. Opin. Struct. Biol. 14, 28–35 (2004).

    Article  CAS  PubMed  Google Scholar 

  24. Keyamura, K., Abe, Y., Higashi, M., Ueda, T. & Katayama, T. DiaA dynamics are coupled with changes in initial origin complexes leading to helicase loading. J. Biol. Chem. 284, 25038–25050 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Abe, Y. et al. Structure and function of DnaA N-terminal domains: specific sites and mechanisms in inter-DnaA interaction and in DnaB helicase loading on oriC. J. Biol. Chem. 282, 17816–17827 (2007).

    Article  CAS  PubMed  Google Scholar 

  26. Felczak, M. M., Simmons, L. A. & Kaguni, J. M. An essential tryptophan of Escherichia coli DnaA protein functions in oligomerization at the E. coli replication origin. J. Biol. Chem. 280, 24627–24633 (2005).

    Article  CAS  PubMed  Google Scholar 

  27. Nishida, S. et al. A nucleotide switch in the Escherichia coli DnaA protein initiates chromosomal replication: evidence from a mutant DnaA protein defective in regulatory ATP hydrolysis in vitro and in vivo. J. Biol. Chem. 277, 14986–14995 (2002).

    Article  CAS  PubMed  Google Scholar 

  28. Felczak, M. M. & Kaguni, J. M. The box VII motif of Escherichia coli DnaA protein is required for DnaA oligomerization at the E. coli replication origin. J. Biol. Chem. 279, 51156–51162 (2004).

    Article  CAS  PubMed  Google Scholar 

  29. Kawakami, H. et al. The exceptionally tight affinity of DnaA for ATP/ADP requires a unique aspartic acid residue in the AAA+ sensor 1 motif. Mol. Microbiol. 62, 1310–1324 (2006).

    Article  CAS  PubMed  Google Scholar 

  30. Iyer, L. M., Leipe, D. D., Koonin, E. V. & Aravind, L. Evolutionary history and higher order classification of AAA+ ATPases. J. Struct. Biol. 146, 11–31 (2004).

    Article  CAS  PubMed  Google Scholar 

  31. Erzberger, J. P., Pirruccello, M. M. & Berger, J. M. The structure of bacterial DnaA: implications for general mechanisms underlying DNA replication initiation. EMBO J. 21, 4763–4773 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Fujikawa, N. et al. Structural basis of replication origin recognition by the DnaA protein. Nucleic Acid Res. 31, 2077–2086 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Lu, M., Campbell, J. L., Boye, E. & Kleckner, N. SeqA: a negative modulator of replication initiation in E. coli. Cell 77, 413–426 (1994).

    Article  CAS  PubMed  Google Scholar 

  34. Slater, S. et al. E. coli SeqA protein binds oriC in two different methyl-modulated reactions appropriate to its roles in DNA replication initiation and origin sequestration. Cell 82, 927–936 (1995).

    Article  CAS  PubMed  Google Scholar 

  35. Fujikawa, N. et al. Structural and biochemical analyses of hemimethylated DNA binding by the SeqA protein. Nucleic Acids Res. 32, 82–92 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Han, J. S., Kang, S., Kim, S. H., Ko, M. J. & Hwang, D. S. Binding of SeqA protein to hemi-methylated GATC sequences enhances their interaction and aggregation properties. J. Biol. Chem. 279, 30236–30243 (2004).

    Article  CAS  PubMed  Google Scholar 

  37. Guarne, A. et al. Crystal structure of a SeqA-N filament: implications for DNA replication and chromosome organization. EMBO J. 24, 1502–1511 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Bach, T., Krekling, M. A. & Skarstad, K. Excess SeqA prolongs sequestration of oriC and delays nucleoid segregation and cell division. EMBO J. 22, 315–323 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Nievera, C., Torgue, J. J., Grimwade, J. E. & Leonard, A. C. SeqA blocking of DnaA-oriC interactions ensures staged assembly of the E. coli pre-RC. Mol. Cell 24, 581–592 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Onogi, T., Niki, H., Yamazoe, M. & Hiraga, S. The assembly and migration of SeqA-Gfp fusion in living cells of Escherichia coli. Mol. Microbiol. 31, 1775–1782 (1999).

    Article  CAS  PubMed  Google Scholar 

  41. Brendler, T., Sawitzke, J., Sergueev, K. & Austin, S. A case for sliding SeqA tracts at anchored replication forks during Escherichia coli chromosome replication and segregation. EMBO J. 19, 6249–6258 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Molina, F. & Skarstad, K. Replication fork and SeqA focus distributions in Escherichia coli suggest a replication hyperstructure dependent on nucleotide metabolism. Mol. Microbiol. 52, 1597–1612 (2004).

    Article  CAS  PubMed  Google Scholar 

  43. Bogan, J. A. & Helmstetter, C. E. DNA sequestration and transcription in the oriC region of Escherichia coli. Mol. Microbiol. 26, 889–896 (1997).

    Article  CAS  PubMed  Google Scholar 

  44. Braun, R. E. & Wright, A. DNA methylation differentially enhances the expression of one of the two E. coli dnaA promoters in vivo and in vitro. Mol. Gen. Genet. 202, 246–250 (1986).

    Article  CAS  PubMed  Google Scholar 

  45. Riber, L. & Løbner-Olesen, A. Coordinated replication and sequestration of oriC and dnaA are required for maintaining controlled once-per-cell-cycle initiation in Escherichia coli. J. Bacteriol. 187, 5605–5613 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Messer, W. & Weigel, C. DnaA initiator—also a transcriptional factor. Mol. Microbiol. 24, 1–6 (1997).

    Article  CAS  PubMed  Google Scholar 

  47. Braun, R. E., O'Day, K. & Wright, A. Autoregulation of the DNA replication gene dnaA in E. coli K-12. Cell 40, 159–169 (1985).

    Article  CAS  PubMed  Google Scholar 

  48. Atlung, T., Løbner-Olesen, A. & Hansen, F. G. Overproduction of DnaA protein stimulates initiation of chromosome and minichromosome replication in Escherichia coli. Mol. Gen. Genet. 206, 51–59 (1987).

    Article  CAS  PubMed  Google Scholar 

  49. Katayama, T., Kubota, T., Kurokawa, K., Crooke, E. & Sekimizu, K. The initiator function of DnaA protein is negatively regulated by the sliding clamp of the E. coli chromosomal replicase. Cell 94, 61–71 (1998).

    Article  CAS  PubMed  Google Scholar 

  50. Kato, J. & Katayama, T. Hda, a novel DnaA-related protein, regulates the replication cycle in Escherichia coli. EMBO J. 20, 4253–4262 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Bochner, B. R. & Ames, B. N. Complete analysis of cellular nucleotides by two-dimensional thin layer chromatography. J. Biol. Chem. 257, 9759–9769 (1982).

    CAS  PubMed  Google Scholar 

  52. Camara, J. E. et al. Hda inactivation of DnaA is the predominant mechanism preventing hyperinitiation of Escherichia coli DNA replication. EMBO Rep. 6, 736–741 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Su'etsugu, M., Shimuta, T., Ishida, T., Kawakami, H. & Katayama, T. Protein associations in DnaA-ATP hydrolysis mediated by the Hda-replicase clamp complex. J. Biol. Chem. 280, 6528–6536 (2005).

    Article  CAS  PubMed  Google Scholar 

  54. Xu, Q. et al. A structural basis for the regulatory inactivation of DnaA. J. Mol. Biol. 385, 368–380 (2009).

    Article  CAS  PubMed  Google Scholar 

  55. Fujimitsu, K. et al. Modes of overinitiation, dnaA gene expression, and inhibition of cell division in a novel cold-sensitive hda mutant of Escherichia coli. J. Bacteriol. 190, 5368–5381 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Felczak, M. M. & Kaguni, J. M. DnaAcos hyperinitiates by circumventing regulatory pathways that control the frequency of initiation in Escherichia coli. Mol. Microbiol. 72, 1348–1363 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Su'etsugu, M., Nakamura, K., Keyamura, K., Kudo, Y. & Katayama, T. Hda monomerization by ADP binding promotes replicase clamp-mediated DnaA-ATP hydrolysis. J. Biol. Chem. 283, 36118–36131 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Onogi, T., Ohsumi, K., Katayama, T. & Hiraga, S. Replication-dependent recruitment of the β-subunit of DNA polymerase III from cytosolic spaces to replication forks in Escherichia coli. J. Bacteriol. 184, 867–870 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Fujimitsu, K., Senriuchi, T. & Katayama, T. Specific genomic sequences of E. coli promote replicational initiation by directly reactivating ADP-DnaA. Genes Dev. 23, 1221–1233 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Sekimizu, K., Yung, B. Y. & Kornberg, A. The dnaA protein of Escherichia coli. Abundance, improved purification, and membrane binding. J. Biol. Chem. 263, 7136–7140 (1988).

    CAS  PubMed  Google Scholar 

  61. Kitagawa, R., Mitsuki, H., Okazaki, T. & Ogawa, T. A novel DnaA protein-binding site at 94.7 min on the Escherichia coli chromosome. Mol. Microbiol. 19, 1137–1147 (1996).

    Article  CAS  PubMed  Google Scholar 

  62. Kitagawa, R., Ozaki, T., Moriya, S. & Ogawa, T. Negative control of replication initiation by a novel chromosomal locus exhibiting exceptional affinity for Escherichia coli DnaA protein. Genes Dev. 12, 3032–3043 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Nozaki, S., Yamada, Y. & Ogawa, T. Initiator titration complex formed at datA with the aid of IHF regulates replication timing in Escherichia coli. Genes Cells 14, 329–341 (2009).

    Article  CAS  PubMed  Google Scholar 

  64. Nozaki, S., Niki, H. & Ogawa, T. Replication initiator DnaA of Escherichia coli changes its assembly form on the replication origin during the cell cycle. J. Bacteriol. 191, 4807–4814 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Paulsson, J. & Chattoraj, D. K. Origin inactivation in bacterial DNA replication control. Mol. Microbiol. 61, 9–15 (2006).

    Article  CAS  PubMed  Google Scholar 

  66. Hansen, F. G., Christensen, B. B. & Atlung, T. The initiator titration model: computer simulation of chromosome and minichromosome control. Res. Microbiol. 142, 161–167 (1991).

    Article  CAS  PubMed  Google Scholar 

  67. Boeneman, K. et al. Escherichia coli DnaA forms helical structures along the longitudinal cell axis distinct from MreB filaments. Mol. Microbiol. 72, 645–657 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Morigen, Molina, F. & Skarstad, K. Deletion of the datA site does not affect once-per-cell-cycle timing but induces rifampin-resistant replication. J. Bacteriol. 187, 3913–3920 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Boye, E. & Løbner-Olesen, A. Bacterial growth control studied by flow cytometry. Res. Microbiol. 142, 131–135 (1991).

    Article  CAS  PubMed  Google Scholar 

  70. Hiraga, S., Ichinose, C., Onogi, T., Niki, H. & Yamazoe, M. Bidirectional migration of SeqA-bound hemimethylated DNA clusters and pairing of oriC copies in Escherichia coli. Genes Cells 5, 327–341 (2000).

    Article  CAS  PubMed  Google Scholar 

  71. Castilla-Llorente, V., Munoz-Espin, D., Villar, L., Salas, M. & Meijer, W. J. Spo0A, the key transcriptional regulator for entrance into sporulation, is an inhibitor of DNA replication. EMBO J. 25, 3890–3899 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Rahn-Lee, L., Gorbatyuk, B., Skovgaard, O. & Losick, R. The conserved sporulation protein YneE inhibits DNA replication in Bacillus subtilis. J. Bacteriol. 191, 3736–3739 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Wagner, J. K., Marquis, K. A. & Rudner, D. Z. SirA enforces diploidy by inhibiting the replication initiator DnaA during spore formation in Bacillus subtilis. Mol. Microbiol. 73, 963–974 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Noirot-Gros, M. F. et al. An expanded view of bacterial DNA replication. Proc. Natl Acad. Sci. USA 99, 8342–8347 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Noirot-Gros, M. F. et al. Functional dissection of YabA, a negative regulator of DNA replication initiation in Bacillus subtilis. Proc. Natl Acad. Sci. USA 103, 2368–2373 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Hayashi, M., Ogura, Y., Harry, E. J., Ogasawara, N. & Moriya, S. Bacillus subtilis YabA is involved in determining the timing and synchrony of replication initiation. FEMS Microbiol. Lett. 247, 73–79 (2005).

    Article  CAS  PubMed  Google Scholar 

  77. Goranov, A. I., Breier, A. M., Merrikh, H. & Grossman, A. D. YabA of Bacillus subtilis controls DnaA-mediated replication initiation but not the transcriptional response to replication stress. Mol. Microbiol. 74, 454–466 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Soufo, C. D. et al. Cell-cycle-dependent spatial sequestration of the DnaA replication initiator protein in Bacillus subtilis. Dev. Cell 15, 935–941 (2008).

    Article  PubMed  CAS  Google Scholar 

  79. Meile, J. C., Wu, L. J., Ehrlich, S. D., Errington, J. & Noirot, P. Systematic localisation of proteins fused to the green fluorescent protein in Bacillus subtilis: identification of new proteins at the DNA replication factory. Proteomics 6, 2135–2146 (2006).

    Article  CAS  PubMed  Google Scholar 

  80. Cho, E., Ogasawara, N. & Ishikawa, S. The functional analysis of YabA, which interacts with DnaA and regulates initiation of chromosome replication in Bacillus subtils. Genes Genet. Syst. 83, 111–125 (2008).

    Article  CAS  PubMed  Google Scholar 

  81. Ogura, Y., Imai, Y., Ogasawara, N. & Moriya, S. Autoregulation of the dnaA-dnaN operon and effects of DnaA protein levels on replication initiation in Bacillus subtilis. J. Bacteriol. 183, 3833–2841 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Moriya, S., Fukuoka, T., Ogasawara, N. & Yoshikawa, H. Regulation of initiation of the chromosomal replication by DnaA-boxes in the origin region of the Bacillus subtilis chromosome. EMBO J. 7, 2911–2297 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Moriya, S., Atlung, T., Hansen, F. G., Yoshikawa, H. & Ogasawara, N. Cloning of an autonomously replicating sequence (ars) from the Bacillus subtilis chromosome. Mol. Microbiol. 6, 309–315 (1992).

    Article  CAS  PubMed  Google Scholar 

  84. Murray, H. & Errington, J. Dynamic control of the DNA replication initiation protein DnaA by Soj/ParA. Cell 135, 74–84 (2008).

    Article  CAS  PubMed  Google Scholar 

  85. Lee, P. S. & Grossman, A. D. The chromosome partitioning proteins Soj (ParA) and Spo0J (ParB) contribute to accurate chromosome partitioning, separation of replicated sister origins, and regulation of replication initiation in Bacillus subtilis. Mol. Microbiol. 60, 853–869 (2006).

    Article  CAS  PubMed  Google Scholar 

  86. Ebersbach, G. & Gerdes, K. Plasmid segregation mechanisms. Annu. Rev. Genet. 39, 453–479 (2005).

    Article  CAS  PubMed  Google Scholar 

  87. Ogura, Y., Ogasawara, N., Harry, E. J. & Moriya, S. Increasing the ratio of Soj to Spo0J promotes replication initiation in Bacillus subtilis. J. Bacteriol. 185, 6316–6324 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Veening, J. W., Murray, H. & Errington, J. A mechanism for cell cycle regulation of sporulation initiation in Bacillus subtilis. Genes Dev. 23, 1959–1570 (2009).

    CAS  Google Scholar 

  89. Quon, K. C., Yang, B., Domian, I. J., Shapiro, L. & Marczynski, G. T. Negative control of bacterial DNA replication by a cell cycle regulatory protein that binds at the chromosome origin. Proc. Natl Acad. Sci. USA 95, 120–125 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Bastedo, D. P. & Marczynski, G. T. CtrA response regulator binding to the Caulobacter chromosome replication origin is required during nutrient and antibiotic stress as well as during cell cycle progression. Mol. Microbiol. 72, 139–154 (2009).

    Article  CAS  PubMed  Google Scholar 

  91. Siam, R. & Marczynski, G. T. Cell cycle regulator phosphorylation stimulates two distinct modes of binding at a chromosome replication origin. EMBO J. 19, 1138–1147 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. McGrath, P. T., Iniesta, A. A., Ryan, K. R., Shapiro, L. & McAdams, H. H. A dynamically localized protease complex and a polar specificity factor control a cell cycle master regulator. Cell 124, 535–547 (2006).

    Article  CAS  PubMed  Google Scholar 

  93. Gorbatyuk, B. & Marczynski, G. T. Regulated degradation of chromosome replication proteins DnaA and CtrA in Caulobacter crescentus. Mol. Microbiol. 55, 1233–1245 (2005).

    Article  CAS  PubMed  Google Scholar 

  94. Collier, J. & Shapiro, L. Feedback control of DnaA-mediated replication initiation by replisome-associated HdaA protein in Caulobacter. J. Bacteriol. 191, 5706–5716 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Lesley, J. A. & Shapiro, L. SpoT regulates DnaA stability and initiation of DNA replication in carbon-starved Caulobacter crescentus. J. Bacteriol. 190, 6867–6880 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Arias, E. E. & Walter, J. C. PCNA functions as a molecular platform to trigger Cdt1 destruction and prevent re-replication. Nature Cell Biol. 8, 84–90 (2006).

    Article  CAS  PubMed  Google Scholar 

  97. Nishitani, H. et al. Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target human Cdt1 for proteolysis. EMBO J. 25, 1126–1136 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Senga, T. et al. PCNA is a cofactor for Cdt1 degradation by CUL4/DDB1-mediated N-terminal ubiquitination. J. Biol. Chem. 281, 6246–6252 (2006).

    Article  CAS  PubMed  Google Scholar 

  99. Ralph, E., Boye, E. & Kearsey, S. E. DNA damage induces Cdt1 proteolysis in fission yeast through a pathway dependent on Cdt2 and Ddb1. EMBO Rep. 7, 1134–1139 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Kim, Y. & Kipreos, E. T. The Caenorhabditis elegans replication licensing factor CDT-1 is targeted for degradation by the CUL-4/DDB-1 complex. Mol. Cell Biol. 27, 1394–1406 (2007).

    Article  CAS  PubMed  Google Scholar 

  101. Shibutani. et al. Intrinsic negative cell cycle regulation provided by PIP box- and Cul4Cdt2-mediated destruction of E2f1 during S phase. Dev. Cell 15, 890–900 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Katayama, T., Takata, M. & Sekimizu, K. CedA is a novel Escherichia coli protein that activates the cell division inhibited by chromosomal DNA overreplication. Mol. Microbiol. 26, 687–697 (1997).

    Article  CAS  PubMed  Google Scholar 

  103. Simmons, L. A., Breier, A. M., Cozzarelli, N. R. & Kaguni, J. M. Hyperinitiation of DNA replication in Escherichia coli leads to replication fork collapse and inviability. Mol. Microbiol. 51, 349–358 (2004).

    Article  CAS  PubMed  Google Scholar 

  104. Zawilak-Pawlik, A. et al. HobA – a novel protein involved in initiation of chromosomal replication in Helicobacter pylori. Mol. Microbiol. 65, 979–994 (2007).

    Article  CAS  PubMed  Google Scholar 

  105. Natrajan, G., Hall, D. R., Thompson, A. C., Gutsche, I. & Terradot, L. Structural similarity between the DnaA-binding proteins HobA (HP1230) from Helicobacter pylori and DiaA from Escherichia coli. Mol. Microbiol. 65, 995–1005 (2007).

    Article  CAS  PubMed  Google Scholar 

  106. Natrajan, G., Noirot-Gros, M. F., Zawilak-Pawlik, A., Kapp, U. & Terradot, L. The structure of a DnaA/HobA complex from Helicobacter pylori provides insight into regulation of DNA replication in bacteria. Proc. Natl Acad. Sci. USA 106, 21115–21120 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We apologize to all researchers in this field whose work could not be cited because of space limitations. Our study is supported mainly by the Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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  1. Kenji Keyamura and Kazuyuki Fujimitsu are at the Department of Molecular Biology, Tsutomu Katayama, Shogo Ozaki, Kyushu University Graduate School of Pharmaceutical Sciences, Fukuoka 812-8582, Japan.,

    Tsutomu Katayama, Shogo Ozaki, Kenji Keyamura & Kazuyuki Fujimitsu

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  1. Tsutomu Katayama
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  2. Shogo Ozaki
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  3. Kenji Keyamura
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  4. Kazuyuki Fujimitsu
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Correspondence to Tsutomu Katayama.

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Entrez Genome Project

Bacillus subtilis

Caenorhabditis elegans

Caulobacter crescentus

Drosophila melanogaster

Escherichia coli

Xenopus laevis

Protein Data Bank

1J1V

2E0G

2Z4S

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Katayama, T., Ozaki, S., Keyamura, K. et al. Regulation of the replication cycle: conserved and diverse regulatory systems for DnaA and oriC. Nat Rev Microbiol 8, 163–170 (2010). https://doi.org/10.1038/nrmicro2314

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