Berlin 2018 – wissenschaftliches Programm

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BP: Fachverband Biologische Physik

BP 9: Postersession I

BP 9.37: Poster

Montag, 12. März 2018, 17:30–19:30, Poster A

Modelling the cell-cycle dependent regulation of p21 after DNA damage — •Isabella-Hilda Mendler and Barbara Drossel — TU Darmstadt, Germany

Ionizing radiation causes DNA double strand breaks and hence threatens the successful division or even the survival of a 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 p21, a potent cyclin-dependent kinase inhibitor that regulates cell-cycle arrest after DNA damage. Recent single-cell experiments showed that the timing and rate of its induction after DNA damage is heterogeneous, with the cell-cycle stage playing a crucial role.

We present a minimalistic nonlinear delay differential equation model for the regulation of p21 by p53 that reproduces the main features of the cell-cycle dependent dynamical behavior of p21 in response to the p53 oscillations following DNA damage. The p53 measurement data are input to the model, and the p21 response is modelled by including cell-cycle dependent protein production and degradation rates. These features enable us to reproduce the observed delay of p21 response in cells that experience the damage in the S phase, as well as the prompt pulse-like response of p21 in cells that are irradiated in G1 and progress to S phase.