Dresden 2017 – wissenschaftliches Programm

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DY: Fachverband Dynamik und Statistische Physik

DY 58: Posters - Networks

DY 58.1: Poster

Donnerstag, 23. März 2017, 17:00–19:30, P1A

Modelling the regulation of p21 by p53 after DNA damage — •Isabella-Hilda Bodea and Barbara Drossel — TU Darmstadt, Germany

Biological cells must constantly respond to different forms of stress. One of the most common sources of cellular stress is ionizing radiation, which causes DNA double strand breaks and hence threatens the successful division or even the survival of the irradiated cell. For this reason, cells react to DNA damages by upregulating the tumor suppressor protein p53, which shows multiple pulses after the occurrence of the damage and activates numerous target proteins. One of the most important target proteins of p53 is CDKN1A (also known as p21), a potent cyclin-dependent kinase inhibitor that regulates cell-cycle arrest after DNA damage. Studies of the CDKN1A dynamics post-DNA damage in single cells revealed heterogeneity in the timing and rate of CDKN1A induction and showed that the cell-cycle stage plays a crucial role in this context.

We present a minimalistic nonlinear ordinary differential equation model for the regulation of p21 by p53 that reproduces the overall dynamical behavior of p21 in response to the p53 oscillations following DNA damage. The model includes cell-cycle dependence of degradation rates and several inhibition mechanisms and reveals the possible ways in which the observed heterogeneous response of p21 can arise.