Non-random segregation of sister chromosomes in Escherichia coli


It has long been known that the 5′ to 3′ polarity of DNA synthesis results in both a leading and lagging strand at all replication forks1. Until now, however, there has been no evidence that leading or lagging strands are spatially organized in any way within a cell. Here we show that chromosome segregation in Escherichia coli is not random but is driven in a manner that results in the leading and lagging strands being addressed to particular cellular destinations. These destinations are consistent with the known patterns of chromosome segregation2,3. Our work demonstrates a new level of organization relating to the replication and segregation of the E. coli chromosome.

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Figure 1: Distinguishing leading and lagging strands.
Figure 2: Visualization of construct.
Figure 3: Construct degradation and localization.
Figure 4: Induction of SbcCD in cephalexin-induced filaments.


  1. 1

    McInerney, P., Johnson, A., Katz, F. & O’Donnell, M. Characterization of a triple DNA polymerase replisome. Mol. Cell 27, 527–538 (2007)

    CAS  Article  Google Scholar 

  2. 2

    Wang, X., Liu, X., Possoz, C. & Sherratt, D. J. The two Escherichia coli chromosome arms locate to separate cell halves. Genes Dev. 20, 1727–1731 (2006)

    CAS  Article  Google Scholar 

  3. 3

    Nielsen, H. J. et al. The Escherichia coli chromosome is organized with the left and right chromosome arms in separate cell halves. Mol. Microbiol. 62, 331–338 (2006)

    CAS  Article  Google Scholar 

  4. 4

    Thanbichler, M. & Shapiro, L. Getting organized—how bacterial cells move proteins and DNA. Nature Rev. Microbiol. 6, 28–40 (2008)

    CAS  Article  Google Scholar 

  5. 5

    Wang, X., Possoz, C. & Sherratt, D. J. Dancing around the divisome: asymmetric chromosome segregation in Escherichia coli . Genes Dev. 19, 2367–2377 (2005)

    CAS  Article  Google Scholar 

  6. 6

    Woldringh, C. L. & Nanninga, N. Structural and physical aspects of bacterial chromosome segregation. J. Struct. Biol. 156, 273–283 (2006)

    CAS  Article  Google Scholar 

  7. 7

    Rocha, E. P. et al. A strand-specific model for chromosome segregation in bacteria. Mol. Microbiol. 49, 895–903 (2003)

    CAS  Article  Google Scholar 

  8. 8

    Eykelenboom, J. K., Blackwood, J. K., Okely, E. & Leach, D. R. SbcCD causes a double-strand break at a DNA palindrome in the Escherichia coli chromosome. Mol. Cell 29, 644–651 (2008)

    CAS  Article  Google Scholar 

  9. 9

    Pinder, D. J., Blake, C. E., Lindsey, J. C. & Leach, D. R. Replication strand preference for deletions associated with DNA palindromes. Mol. Microbiol. 28, 719–727 (1998)

    CAS  Article  Google Scholar 

  10. 10

    Skarstad, K. & Boye, E. Degradation of individual chromosomes in recA mutants of Escherichia coli . J. Bacteriol. 175, 5505–5509 (1993)

    CAS  Article  Google Scholar 

  11. 11

    Mason, D. J. & Powelson, D. M. Nuclear division as observed in live bacteria by a new technique. J. Bacteriol. 71, 474–479 (1956)

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12

    Khlebnikov, A. et al. Homogeneous expression of the P(BAD) promoter in Escherichia coli by constitutive expression of the low-affinity high-capacity AraE transporter. Microbiology 147, 3241–3247 (2001)

    CAS  Article  Google Scholar 

  13. 13

    Darmon, E. et al. SbcCD regulation and localization in Escherichia coli . J. Bacteriol. 189, 6686–6694 (2007)

    CAS  Article  Google Scholar 

  14. 14

    Cairns, J. Mutation selection and the natural history of cancer. Nature 255, 197–200 (1975)

    ADS  CAS  Article  Google Scholar 

  15. 15

    Rando, T. A. The immortal strand hypothesis: segregation and reconstruction. Cell 129, 1239–1243 (2007)

    CAS  Article  Google Scholar 

  16. 16

    Kiel, M. J. et al. Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU. Nature 449, 238–242 (2007)

    ADS  CAS  Article  Google Scholar 

  17. 17

    Waghmare, S. K. et al. Quantitative proliferation dynamics and random chromosome segregation of hair follicle stem cells. EMBO J. 27, 1309–1320 (2008)

    CAS  Article  Google Scholar 

  18. 18

    Lansdorp, P. M. Immortal strands? Give me a break. Cell 129, 1244–1247 (2007)

    CAS  Article  Google Scholar 

  19. 19

    Lew, D. J., Burke, D. J. & Dutta, A. The immortal strand hypothesis: how could it work? Cell 133, 21–23 (2008)

    CAS  Article  Google Scholar 

  20. 20

    Niki, H., Yamaichi, Y. & Hiraga, S. Dynamic organization of chromosomal DNA in Escherichia coli . Genes Dev. 14, 212–223 (2000)

    CAS  PubMed  PubMed Central  Google Scholar 

  21. 21

    Yamaichi, Y. & Niki, H. migS, a cis-acting site that affects bipolar positioning of oriC on the Escherichia coli chromosome. EMBO J. 23, 221–233 (2004)

    CAS  Article  Google Scholar 

  22. 22

    Thanbichler, M. & Shapiro, L. Chromosome organization and segregation in bacteria. J. Struct. Biol. 156, 292–303 (2006)

    CAS  Article  Google Scholar 

  23. 23

    Danilova, O. et al. MukB colocalizes with the oriC region and is required for organization of the two Escherichia coli chromosome arms into separate cell halves. Mol. Microbiol. 65, 1485–1492 (2007)

    CAS  Article  Google Scholar 

  24. 24

    Gitai, Z. et al. MreB actin-mediated segregation of a specific region of a bacterial chromosome. Cell 120, 329–341 (2005)

    CAS  Article  Google Scholar 

  25. 25

    Kruse, T. et al. Actin homolog MreB and RNA polymerase interact and are both required for chromosome segregation in Escherichia coli . Genes Dev. 20, 113–124 (2006)

    CAS  Article  Google Scholar 

  26. 26

    Karczmarek, A. et al. DNA and origin region segregation are not affected by the transition from rod to sphere after inhibition of Escherichia coli MreB by A22. Mol. Microbiol. 65, 51–63 (2007)

    CAS  Article  Google Scholar 

  27. 27

    Lemon, K. P. & Grossman, A. D. Localization of bacterial DNA polymerase: evidence for a factory model of replication. Science 282, 1516–1519 (1998)

    CAS  Article  Google Scholar 

  28. 28

    Rossi, M. L., Purohit, V., Brandt, P. D. & Bambara, R. A. Lagging strand replication proteins in genome stability and DNA repair. Chem. Rev. 106, 453–473 (2006)

    CAS  Article  Google Scholar 

  29. 29

    Reyes-Lamothe, R., Possoz, C., Danilova, O. & Sherratt, D. J. Independent positioning and action of Escherichia coli replisomes in live cells. Cell 133, 90–102 (2008)

    CAS  Article  Google Scholar 

  30. 30

    Possoz, C., Filipe, S. R., Grainge, I. & Sherratt, D. J. Tracking of controlled Escherichia coli replication fork stalling and restart at repressor-bound DNA in vivo . EMBO J. 25, 2596–2604 (2006)

    CAS  Article  Google Scholar 

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We thank D. Sherratt for the gifts of plasmids pWX6, pLau43 and pLau44. We also thank E. Darmon and J. Blackwood for reading the manuscript. This work was supported by the Medical Research Council.

Author Contributions M.A.W. and D.R.F.L. conceived and designed the experiments; M.A.W. constructed all strains and plasmids apart from pDL1625, pDL1709 and pDL2542, which were constructed by J.K.E., E.W. and M.A.L.-V., respectively; M.A.W. performed the experiments; M.A.W. and D.R.F.L. analysed the data and wrote the paper.

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Correspondence to David R. F. Leach.

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White, M., Eykelenboom, J., Lopez-Vernaza, M. et al. Non-random segregation of sister chromosomes in Escherichia coli. Nature 455, 1248–1250 (2008).

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