Modelling the effect of phosphorylation on the circadian clock of Drosophila

Journal of Theoretical Biology
Sebastián Risau-Gusman, Pablo M Gleiser

Abstract

It is by now well known that, at the molecular level, the core of the circadian clock of most living species is a negative feedback loop where some proteins inhibit their own transcription. However, it has recently been shown that post-translational processes, such as phosphorylations, are essential for a correct timing of the clock. Depending on which sites of a circadian protein are phosphorylated, different properties such as degradation, nuclear localization and repressing power can be altered. Furthermore, phosphorylation domains can be related in a positive way, giving rise to consecutive phosphorylations, or in a negative way, hindering phosphorylation at other domains. Here we present a simple mathematical model of a circadian protein having two mutually exclusive domains of phosphorylation. We show that the system has limit cycles that arise from a unique fixed point through a Hopf bifurcation. We find a set of parameters, with realistic values, for which the limit cycle has the same period as the wild type circadian oscillations of the fruit fly. The domains act as a switch, in the sense that alterations in their phosphorylation can alter the period of circadian oscillation in opposite ways, increasing or decreasing t...Continue Reading

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Citations

Sep 7, 2014·Journal of Theoretical Biology·Stephanie R TaylorSarah M Harmon
Oct 3, 2019·Physical Review. E·Paula S Nieto, C A Condat

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