Mathematical Modelling of p53 Signalling during DNA Damage Response: A Survey

Abstract

No gene has garnered more interest than p53 since its discovery over 40 years ago. In the last two decades, thanks to seminal work from Uri Alon and Ghalit Lahav, p53 has defined a truly synergistic topic in the field of mathematical biology, with a rich body of research connecting mathematic endeavour with experimental design and data. In this review we survey and distill the extensive literature of mathematical models of p53. Specifically, we focus on models which seek to reproduce the oscillatory dynamics of p53 in response to DNA damage. We review the standard modelling approaches used in the field categorising them into three types: time delay models, spatial models and coupled negative-positive feedback models, providing sample model equations and simulation results which show clear oscillatory dynamics. We discuss the interplay between mathematics and biology and show how one informs the other; the deep connections between the two disciplines has helped to develop our understanding of this complex gene and paint a picture of its dynamical response. Although yet more is to be elucidated, we offer the current state-of-the-art understanding of p53 response to DNA damage.

The ups and downs of biological oscillators: A comparison of time-delayed negative feedback mechanisms

“…More generally, a feedback that activates degradation (Fig. 1(h)) can also be found in other biological systems, for example in the dynamics of the tumor repressor protein p53 in response to DNA damage (Eliaš and Macnamara 2021;Lahav et al 2004;Lev Bar-Or et al 2000).…”

Natural Products Against Renal Fibrosis via Modulation of SUMOylation

“…As a tumor suppressor, p53 could safeguard the genome and prevent malignant transformation by halting the cell cycle and promoting apoptosis (Jiang et al, 2021;Thoms and Stark, 2021). p53 is increased under stimulation, and then upregulates the expression of pro-apoptotic genes (Eliaš and Macnamara, 2021). SUMOylated p53 could bind to the antiapoptotic factor Bax and Bcl-2, and lead to apoptosis (Nowakowski et al, 2021).…”

The ups and downs of biological oscillators: a comparison of time-delayed negative feedback mechanisms

“…Interestingly, an equivalent equation has already been used by Mackey & Glass [31] to model the variation of CO 2 levels in the blood. More generally, a feedback that activates degradation (figure 1 h ) can also be found in other biological systems, for example in the dynamics of the tumour repressor protein p53 in response to DNA damage [32–34].…”