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Model of DNA Dynamics and Replication

Abstract

Before DNA replication can be initiated a definite number of adenosine triphosphate (ATP) containing pre-replication protein complexes (pre-RCs) must be assembled and bound to DNA like in a super-critical mass. A chemically driven dynamics of the Ginzburg-Landau (GL) type is derived, using the non-equilibrium equation for binding of pre-RCs to DNA and a probabilistic conformational distribution of these protein complexes. This dynamics, in which the DNA-protein system behaves like a nonlinear elastically braced string (NEBS), can control the cell cycle via conformational transitions such that G2 cells contain exactly twice as much DNA as G1 cells. After adjustment of previously-made derivations, the model is compared with cell growth data from the T lymphocyte MLA-144.

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References

  1. Kelly, T.J. and Brown, G.W.: Regulation of Chromosome Replication, Annu. Rev. Biochem. 69 (2000), 829–880.

    Article  Google Scholar 

  2. Sherr, C.J.: The Pezcoller Lecture: Cancer Cell Cycles Revisited, Cancer Res. 60 (2000), 3689–3695.

    Google Scholar 

  3. Matsson, L.: DNA Replication and Cell Cycle Progression Regulated by Long Range Interaction between Protein Complexes Bound to DNA, J. Biol. Phys. 27 (2001), 329–359.

    Article  Google Scholar 

  4. Smith, K.A.: The Interleukin-2 Receptor, Annu. Rev. Cell Biol. 5 (1989), 157–173.

    Article  Google Scholar 

  5. Cantrell, C.A. and Smith, K.A.: The Interleukin-2 T-Cell System: A New Cell Growth Model, Science 224 (1984), 1312–1316.

    ADS  Google Scholar 

  6. Dyson, N.: The Regulation of E2F by pRB-Family Proteins, Genes & Dev. 12 (1998), 2245–2262.

    Google Scholar 

  7. Harbour, J.W. and Dean, D.C.: The Rb/E2F Pathway: Expanding Roles and Emerging Paradigms, Genes & Dev. 14 (2000), 2393–2409.

    Google Scholar 

  8. Helin, K.: Regulation of Cell Proliferation by the E2F Transcription Factors, Curr. Opin. Gen. & Dev. 8 (1998), 28–35.

    Google Scholar 

  9. Dutta, A. and Bell, S.P.: Initiation of DNA Replication in Eukaryotic Cells, Annu. Rev. Cell Dev. Biol. 13 (1997), 293–332.

    Article  Google Scholar 

  10. Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K. and Walter, P.: Molecular Biology of the Cell, Garland Sci., New York 2002, p. 1006.

  11. Bell, S.P. and Stillman, B.: ATP-Dependent Recognition of Eukaryotic Origins of DNA Replication by a Multiprotein Complex, Nature 357 (1992), 128–134.

    ADS  Google Scholar 

  12. Doi, M. and Edwards, S.F.: The Theory of Polymer Dynamics, Clarendon Press, Oxford, 1986.

    Google Scholar 

  13. Wartell, R.M. and Benight, A.S.: Thermal Denaturation of DNA Molecules: A Comparison of Theory with Experiment, Phys. Rep. 126 (1985), 67–107.

    Article  ADS  Google Scholar 

  14. Jackiw, R.: Quantum Meaning of Classical Field Theory, Rev. Mod. Pys. 49 (1977), 681–706.

    ADS  MathSciNet  Google Scholar 

  15. Matsson, L., Sa-yakanit, V. and Boribarn, S.: Lyotropic Ion Channel Current Model Compared with Ising Model, J. Biol. Phys. 31 (2005) 525–532.

    Google Scholar 

  16. Morse, P. and Feshbach, H.: Methods of Mathematical Physics Part I, McGraw-Hill, New-York, 1953.

    Google Scholar 

  17. Matsson, L.: Response Theory for Non-Stationary Ligand-Receptor Interaction and a Solution to the Growth Signal Firing Problem, J. Theor. Biol. 180 (1996), 93–104.

    Article  Google Scholar 

  18. Grosberg, A.Y. and Khokhlov, A.R.: Statistical Physics of Macromolecules, AIP, New York, 1994.

    Google Scholar 

  19. Case, R.B., Chang, Y.-P., Smith, S.B., Gore, J., Cozzarelli, N.R. and Bustamante, C.: The Bacterial Condensin MukBEF Compacts DNA into a Repetitive, Stable Structure, Science 305 (2004), 222–227.

    Article  ADS  Google Scholar 

  20. Matsson, L.: Long Range Interaction between Protein Complexes in DNA Controls Replication and Cell Cycle Progression, J. Biol. Syst. 9 (2001), 41–65.

    Google Scholar 

  21. Bustamante, C., Marko, J.F., Siggia, E.D. and Smith, S.B.: Entropic Elasticity of λ -Phage DNA, Science 265 (1994), 1599–1600.

    ADS  Google Scholar 

  22. Wiegel, F.W.: Introduction to Path-Integral Methods in Physics and Polymer Science, World Scientific, Singapore, 1986.

    Google Scholar 

  23. Poland, D. and Scheraga, H.A.: Occurrence of a Phase Transition in Nucleic Acid Model, J. Chem. Phys. 45 (1966), 1456–1463.

    Google Scholar 

  24. Poland, D. and Scheraga, H.A.: Phase Transitions in One Dimension and the Helix-Coil Transition in Polyamino Acids, J. Chem. Phys. 45 (1966), 1464–1469.

    Google Scholar 

  25. Fischer, M.E.: Effect of Excluded Volume on Phase Transitions in Biopolymers, J. Chem. Phys. 45 (1966), 1469–1473.

    Google Scholar 

  26. Peyrard, M. and Bishop, A.R.: Statistical Mechanics of a Nonlinear Model for DNA Denaturation, Phys. Rev. Lett. 62 (1989), 2755–2758.

    Article  ADS  Google Scholar 

  27. Frauenfelder, H., Wolynes, P.G. and Austin, R.H.: Biological Physics, Rev. Mod. Phys. 71 (1999), S419–S430.

    Article  Google Scholar 

  28. Smith, K.A.: Determining to Divide: How do Cells Decide? J. Biol. Phys. 31 (2005), 261–272.

    Google Scholar 

  29. Ekholm-Reed, S., Mendez, J., Tedesco, D., Zetterberg, A., Stillman, B. and Reed, S.I.: Deregulation of Cyclin E in Human Cells Interferes with Prereplication Complex Assembly, J. Cell. Biol. 165 (2004), 789–800.

    Article  Google Scholar 

  30. Matsson, L.: Soliton Growth-Signal Transduction in Topologically Quantized T Cells, Phys. Rev. E 48 (1993), 2217–2231.

    Google Scholar 

  31. Kramers, H.A.: Statistics of the Two-Dimensional Ferromagnet. Part I, Phys. Rev. 60 (1941), 252–262.

    ADS  MATH  MathSciNet  Google Scholar 

  32. Jarzynski, C.: Nonequilibrium Equality for Free Energy Differences, Phys. Rev. Lett. 78 (1997), 2690–2693.

    Article  ADS  Google Scholar 

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Correspondence to Leif Matsson.

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Matsson, L. Model of DNA Dynamics and Replication. J Biol Phys 31, 303–321 (2005). https://doi.org/10.1007/s10867-005-4635-1

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Key words

  • DNA replication
  • cell cycle regulation
  • DNA dynamics
  • commitment
  • initiation
  • termination
  • DNA condensation
  • DNA conformation
  • DNA folding
  • DNA compaction
  • DNA packing
  • pre-replication complex
  • initiator protein assembly
  • origin recognition
  • non-equilibrium dynamics
  • Ginzburg-Landau model
  • elastically braced string
  • reaction coordinate