Mitotic Oscillators as MP Graphs

  • Giuditta Franco
  • Pietro Hiram Guzzi
  • Vincenzo Manca
  • Tommaso Mazza
Part of the Lecture Notes in Computer Science book series (LNCS, volume 4361)


This paper proposes a model in terms of metabolic P graphs of a few important processes occurring during the biological phase where the choice is made to begin again mitosis or to arrest it. The cellular processes during this phase turn out to be especially interesting in the case of DNA damage, which triggers a specific destruction of Cdc25A phosphatase. It has important implications to understand the role of cell cycle checkpoints and the mechanism(s) guiding the proliferation of UV-resistant tumored cells. The formalism of metabolic P graphs highlights the relevant information of the biological network dynamics, and the individuation of few parameters rules the basic mechanisms of Cdc25A degradation, involving a couple of important mitotic oscillators.


Output Gate Membrane Computing Complex Reaction Network Biological Phase Stoichiometric Network Analysis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Barbacari, N., Profir, A., Zelinschi, C.: Gene regulatory network modelling by means of membrane systems. In: Freund, R., Lojka, G., Oswald, M., Păun, G. (eds.) Pre-proceedings of the 6th International Workshop on Membrane Computing, Vienna, Austria, July 18-21, 2005, pp. 162–178 (2005)Google Scholar
  2. 2.
    Bartek, J., Lukas, J.: Pathways governing g1/s transition and their response to DNA damage. FEBS Lett. 3(490), 117–122 (2001)CrossRefGoogle Scholar
  3. 3.
    Bernardini, F., Gheorghe, M., Krasnogor, N., Muniyandi, R.C., Jesús Pérez-Jímenez, M., Romero-Campero, F.J.: On P systems as a modelling tool for biological systems. In: Freund, R., Păun, G., Rozenberg, G., Salomaa, A. (eds.) WMC 2005. LNCS, vol. 3850, pp. 114–133. Springer, Heidelberg (2006)CrossRefGoogle Scholar
  4. 4.
    Bianco, L., Fontana, F., Franco, G., Manca, V.: P systems for biological dynamics. In: Ciobanu, G., Păun, G., Perez-Jimenez, M.J. (eds.) Applications of Membrane Computing, Ch. 3, pp. 81–126. Springer, Heidelberg (2006)Google Scholar
  5. 5.
    Bianco, L., Fontana, F., Manca, V.: Metabolic algorithm with time-varying reaction maps. In: Proceedings of the Third Brainstorming Week on Membrane Computing, Sevilla, Spain, pp. 43–61 (February 2005)Google Scholar
  6. 6.
    Fontana, F., Bianco, L., Manca, V.: P systems and the modeling of biochemical oscillations. In: Freund, R., Păun, G., Rozenberg, G., Salomaa, A. (eds.) WMC 2005. LNCS, vol. 3850, pp. 199–208. Springer, Heidelberg (2006)CrossRefGoogle Scholar
  7. 7.
    Bianco, L., Fontana, F., Manca, V.: P systems with reaction maps. International Journal of Foundations of Computer Science (to appear, 2006)Google Scholar
  8. 8.
    Bianco, L., Manca, V.: Symbolic generation and representation of complex oscillations. International Journal of Computer Mathematics 17(1), 27–48 (2006)MATHMathSciNetGoogle Scholar
  9. 9.
    Chopin, V., Toillon, R.A., Jouy, N.: P21(waf1/cip1) is dispensable for g1 arrest, but indispensable for apoptosis induced by sodium butyrate in mcf-7 breast cancer cells. Oncogene 23(1), 21–29 (2004)CrossRefGoogle Scholar
  10. 10.
    Clark, B.L.: Stability of complex reaction networks. Adv. Chem. Phys. 43, 1–216 (1983)CrossRefGoogle Scholar
  11. 11.
    D’Anna, J., Valdez, J.G., Habbersett, R.C., Crissman, H.A.: Association of g1/s-phase and late s-phase checkpoints with regulation of cyclin-dependent kinases in chinese hamster ovary cells. Radiat. Res. 148, 260–271 (1997)CrossRefGoogle Scholar
  12. 12.
    Nakayama, K.I., et al.: Regulation of the cell cycle at the g1-s transition by proteolysis of cyclin e and p27kip1. Biochem. Biophys. Res. Commun. 4(282), 853–860 (2001)CrossRefGoogle Scholar
  13. 13.
    Falck, J., Mailand, N., Syljuåsen, R.G., Bartek, J., Lukas, J.: The atm-chk2-cdc25a checkpoint pathway guards against radioresistant DNA synthesis. Nature 410(6830), 842–847 (2001)CrossRefGoogle Scholar
  14. 14.
    Jinno, S., Suto, K., Nagata, A., Igarashi, M., Kanaoka, Y., Nojima, H., Okayama, H.: Cdc25a is a novel phosphatase functioning early in the cell cycle. EMBO J. 13, 1549–1556 (1994)Google Scholar
  15. 15.
    Mailand, N., Falck, J., Lukas, C., Syljuåsen, R.G., Welcker, M., Bartek, J., Lukas, J.: Rapid destruction of human cdc25a in response to DNA damage. Science 288(5470), 1425–1429 (2000)CrossRefGoogle Scholar
  16. 16.
    Manca, V.: Topics and problems in metabolic p systems. In: Fourth Brainstorming on Membrane Computing, Sevilla, Spain (2006)Google Scholar
  17. 17.
    Manca, V., Bianco, L.: Biological networks in metabolic p system (submitted)Google Scholar
  18. 18.
    Manca, V., Bianco, L., Fontana, F.: Evolution and oscillation in P systems: Applications to biological phenomena. In: Mauri, G., Păun, G., Jesús Pérez-Jímenez, M., Rozenberg, G., Salomaa, A. (eds.) WMC 2004. LNCS, vol. 3365, pp. 63–84. Springer, Heidelberg (2005)CrossRefGoogle Scholar
  19. 19.
    Nilssen, E.A., Synnes, M., Kleckner, N., Grallert, B., Boye, E.: Intra-g1 arrest in response to uv irradiation in fission yeast. Proc. Natl. Acad. Sci. 100(19), 10758–10763 (2003)CrossRefGoogle Scholar
  20. 20.
    Păun, G.: Membrane Computing. An Introduction. Springer, Heidelberg (2002)MATHGoogle Scholar
  21. 21.
    Segel, L.A., Cohen, I.R.: Design Principles for the Immune System and Other Distributed Autonomous Systems. Santa Fe Institute Studies in the Sciences of Complexity. Oxford University Press, Oxford (2001)Google Scholar
  22. 22.
    Suzuki, Y., Tanaka, H.: Modelling p53 signaling pathways by using multiset processing. In: Ciobanu, G., Pérez-Jiménez, M.J., Păun, G. (eds.) Applications of Membrane Computing. Natural Computing Series, pp. 203–214. Springer, Berlin (2006)Google Scholar
  23. 23.
    Waldman, T., Kinzler, K.W., Vogelstein, B.: p21 is necessary for the p53-mediated g1 arrest in human cancer cells. Cancer Research 55(22), 5187–5190 (1995)Google Scholar
  24. 24.
    Zhao, H., Watkins, J.L., Piwnica-Worms, H.: Disruption of the checkpoint kinase 1/cell division cycle 25a pathway abrogates ionizing radiation-induced s and g2 checkpoints. Proc. Natl. Acad. Sci. 99, 14795–14800 (2002)CrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  • Giuditta Franco
    • 1
  • Pietro Hiram Guzzi
    • 2
  • Vincenzo Manca
    • 1
  • Tommaso Mazza
    • 2
  1. 1.Department of Computer ScienceUniversity of VeronaItaly
  2. 2.Magna Græcia University of CatanzaroItaly

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