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The Resection Mechanism Promotes Cell Survival After Exposure to IR

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Man–Machine Interactions 4

Part of the book series: Advances in Intelligent Systems and Computing ((AISC,volume 391))

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Abstract

Ataxia telangiectasia mutated (ATM) protein kinase detects double-strand breaks (DSBs) caused by such environmental factors like ionizing radiation (IR), while ataxia telangiectasia mutated and Rad-3 related (ATR) is activated by the presence of single-stranded DNA areas (ssDNA). Moreover, biological reports show that ATR can be also activated in DSBs repair pathway. Based on experimental reports, we confirmed that the factor responsible for ATR activation may be ssDNA formedS after resection of DSBs by repair complexes. In this study, we propose a novel stochastic mathematical model of ATR-ATM-p53 pathways. The model demonstrates the process of resection and helps to explain the impact of the investigated modules on DNA damages repair. Our results show that the resection of DNA ends accelerates DNA damage repair. Disorders in the mechanisms of DNA repair and resection cause decrease in viability of cells population.

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References

  1. Batchelor, E., Loewer, A., Mock, C., Lahav, G.: Stimulus-dependent dynamics of p53 in single cells. Mol. Syst. Biol. 7(1), 488 (2011)

    Article  Google Scholar 

  2. Ciccia, A., Elledge, S.J.: The DNA damage response: making it safe to play with knives. Mol. Cell 40(2), 179–204 (2010)

    Article  Google Scholar 

  3. Gillespie, D.T.: Exact stochastic simulation of coupled chemical reactions. J. Phys. Chem. 81(25), 2340–2361 (1977)

    Article  Google Scholar 

  4. Haseltine, E.L., Rawlings, J.B.: Approximate simulation of coupled fast and slow reactions for stochastic chemical kinetics. J. Chem. Phys. 117(15), 6959–6969 (2002)

    Article  Google Scholar 

  5. Jazayeri, A., Falck, J., Lukas, C., Bartek, J., Smith, G.: ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks. Nat. Cell Biol. 8(1), 37–45 (2006)

    Article  Google Scholar 

  6. Jonak, K., Jedrasiak, K., Polanski, A., Puszynski, K.: Aplication of image processing in proteomics: automatic analysis of 2-D gel electrophoresis images from western blot assay. In: Bolc, L., Tadeusiewicz, R., Chmielewski, L.J., Wojciechowski, K. (eds.) Computer Vision and Graphics. LNCS, vol. 7594, pp. 433–440. Springer, Berlin (2012)

    Chapter  Google Scholar 

  7. Kim, D.H., Rho, K., Kim, S.: A theoretical model for p53 dynamics. Identifying optimal therapeutic strategy for its activation and stabilization. Cell Cycle 8(22), 3707–3716 (2006)

    Article  Google Scholar 

  8. Kracikova, M., Akiri, G., George, A., Sachidanandam, R., Aaronson, S.: A threshold mechanism mediates p53 cell fate decision between growth arrest and apoptosis. Cell Death Differ. 20(4), 576–588 (2013)

    Article  Google Scholar 

  9. Kurpas, M., Jonak, K., Puszynski, K.: Simulation analysis of the ATR module as a detector of UV-induced DNA damage. In: Piętka, E., Kawa, J., Wieclawek, W. (eds.) Information Technologies in Biomedicine, vol. 3, AISC, vol. 283, pp. 317–326. Springer, Switzerland (2014)

    Google Scholar 

  10. Lobrich, M., Rydberg, B., Cooper, P.: Repair of x-ray-induced DNA doublestrand breaks in specific Not I restriction fragments in human fibroblasts: joining of correct and incorrect ends. Proc. Natl. Acad. Sci. 92(26), 12050–12054 (1995)

    Article  Google Scholar 

  11. Mihara, M., Erster, S., Zaika, A., Petrenko, O., Chittenden, T.: p53 has a direct apoptogenic role at the mitochondria. Mol. Cell 11(3), 577–590 (2003)

    Article  Google Scholar 

  12. Mouri, K., Nacher, J., Akutsu, T.: A mathematical model for the detection mechanism of DNA double-strand breaks depending on autophosphorylation of ATM. PlosOne 4(4), e5131 (2006)

    Article  Google Scholar 

  13. Puszynski, K., Hat, B., Lipniacki, T.: Oscillations and bistability in the stochastic model of p53 regulation. J. Theor. Biol. 254(2), 452–465 (2008)

    Article  Google Scholar 

  14. Puszynski, K., Jonak, K., Kurpas, M., Janus, P., Szoltysek, K.: Analysis of ATM signaling pathway as an activator of p53 and NF-kB regulatory modules and the role of PPM1D. In: IWBBIO 2014, pp. 1471–1482. Granada, Spain (2014)

    Google Scholar 

  15. Rodriguez, A., Sosa, D., Torres, L., Molina, B., Frias, S., Mendoza, L.: A Boolean network model of the FA/BRCA pathway. Bioinformatics 28(6), 858–866 (2012)

    Article  Google Scholar 

  16. Rothkamm, K., Lobrich, M.: Evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses. Proc. Natl. Acad. Sci. 100(9), 5057–5062 (2003)

    Article  Google Scholar 

  17. Sun, T., Yang, W., Liu, J., Shen, P.: Modeling the basal dynamics of P53 system. PlosOne 6(11), e27882 (2011)

    Article  Google Scholar 

  18. Zhang, H.P., Liu, F., Wang, W.: Two-phase dynamics of p53 in the DNA damage response. Proc. Natl. Acad. Sci. 108(22), 8990–8995 (2011)

    Article  Google Scholar 

  19. Zhou, Y., Caron, P., Legube, G., Paull, T.: Quantitation of DNA double-strand break resection intermediates in human cells. Nucleic Acids Res. 42(3), e19 (2014)

    Article  Google Scholar 

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Acknowledgments

This project was funded by the Polish National Center for Science granted by decision number DEC-2012/05/D/ST7/02072.

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Authors and Affiliations

  1. Institute of Automatic Control, Silesian University of Technology, Gliwice, Poland

    Monika Kurpas, Katarzyna Jonak & Krzysztof Puszynski

Authors
  1. Monika Kurpas
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  2. Katarzyna Jonak
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  3. Krzysztof Puszynski
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Corresponding author

Correspondence to Monika Kurpas .

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Editors and Affiliations

  1. Institute of Informatics, Silesian University of Technology, Gliwice, Poland

    Aleksandra Gruca

  2. Institute of Informatics, Silesian University of Technology, Gliwice, Poland

    Agnieszka Brachman

  3. Institute of Informatics, Silesian University of Technology, Gliwice, Poland

    Stanisław Kozielski

  4. Institute of Informatics, Silesian University of Technology, Gliwice, Poland

    Tadeusz CzachĂłrski

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Kurpas, M., Jonak, K., Puszynski, K. (2016). The Resection Mechanism Promotes Cell Survival After Exposure to IR. In: Gruca, A., Brachman, A., Kozielski, S., Czachórski, T. (eds) Man–Machine Interactions 4. Advances in Intelligent Systems and Computing, vol 391. Springer, Cham. https://doi.org/10.1007/978-3-319-23437-3_19

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  • DOI: https://doi.org/10.1007/978-3-319-23437-3_19

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-23436-6

  • Online ISBN: 978-3-319-23437-3

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