DNA Damage Detection and its Impact on the Cell Cycle

Monika Kurpas, Katarzyna Jonak, Krzysztof Puszyński

2014

Abstract

During evolution number of mechanisms that protect cells from damages evolved to prevent their death and lesions transformation to future generations. For efficient repair it is necessary to detect damages quickly and then transfer the signal to other components of cells. This process takes place in a manner specific to the type of lesion. ATR (ataxia telangiectasia mutated and Rad3-related) module is activated by the presence of DNA single stranded breaks (SSBs) in cell, which are caused by resection of various types of lesions or by stalled replication forks. Double strand breaks (DSBs) are detected indirectly by ataxia telangiectasia mutated (ATM). These proteins are involved in the activation of the signaling cascade, as a result of which tumor suppressor p53 is activated and decision about future fate of cells is taken. If the damage is too extensive cell undergoes apoptosis. If damage is repairable, the cell cycle is arrested and damage repair occurs. Current status of DNA is controlled in cell cycle checkpoints. Cell cycle arrest requires signal from the ATM or ATR and Chk1 and Chk2 (checkpoint kinases). At this point, we have created mathematical models of ATR-p53 and ATM-p53 signaling pathways. We plan to combine the developed DNA damage detection pathways and connect them with the cell cycle. Our purpose is to examine the impact of ATM-ATR-p53 path on the cell cycle and examine influence of cell cycle on this path. We also plan to investigate how disabling of selected interactions between molecules may influence the DNA damage response system.

References

  1. Ciccia, A. and Elledge, S. J. (2010). The DNA Damage Response: Making It Safe to Play with Knives. Molecular Cell, 40:179-204.
  2. Cooper, G. M. (2000). The Eukaryotic Cell Cycle. ASM Press, Washington, D.C, 2 edition.
  3. Gartel, A. L. and Radhakrishnan, S. K. (2005). Lost in Transcription: p21 Repression, Mechanisms, and Consequences. Cancer Research, 65:3980-3985.
  4. Gillespie, D. T. (1977). Exact stochastic simulation of coupled chemical reactions. The Journal of Physical Chemistry, 81(25):2340-2361.
  5. Haseltine, E. L. and Rawlings, J. B. (2002). Approximate simulation of coupled fast and slow reactions for stochastic chemical kinetics. Journal of Chemical Physic, 117(15):6959-6969.
  6. Kohn, K. W. (2002). Genomic Instability and DNA Repair. In Alison, M. R., editor, The Cancer Handbook. 2 edition.
  7. Orlando, D. A., Lin, C. Y., Bernard, A., Wang, J. Y., Socolar, J. E. S., Iversen, E. S., J., H. A., and Haase, S. B. (2008). Global control of cell-cycle transcription by coupled CDK and network oscillators. Nature, 453:944-947.
  8. Puszynski, K., Hat, B., and Lipniacki, T. (2008). Oscillations and bistability in the stochastic model of p53 regulation. Journal of Theoretical Biology, 254:452- 465.
  9. Shapiro, G. I. and Harper, J. W. (1999). Anticancer drug targets: cell cycle and checkpoint control. The Journal of Clinical Investigation, 104(12):1645-1653.
  10. Shimada, M. and Nakanishi, M. (2013). Response to DNA damage: why do we need to focus on protein phosphatases? Frontiers in Oncology, 3.
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Paper Citation


in Harvard Style

Kurpas M., Jonak K. and Puszyński K. (2014). DNA Damage Detection and its Impact on the Cell Cycle . In Doctoral Consortium - DCBIOSTEC, (BIOSTEC 2014) ISBN Not Available, pages 67-73


in Bibtex Style

@conference{dcbiostec14,
author={Monika Kurpas and Katarzyna Jonak and Krzysztof Puszyński},
title={DNA Damage Detection and its Impact on the Cell Cycle},
booktitle={Doctoral Consortium - DCBIOSTEC, (BIOSTEC 2014)},
year={2014},
pages={67-73},
publisher={SciTePress},
organization={INSTICC},
doi={},
isbn={Not Available},
}


in EndNote Style

TY - CONF
JO - Doctoral Consortium - DCBIOSTEC, (BIOSTEC 2014)
TI - DNA Damage Detection and its Impact on the Cell Cycle
SN - Not Available
AU - Kurpas M.
AU - Jonak K.
AU - Puszyński K.
PY - 2014
SP - 67
EP - 73
DO -