Positive feedbacks contribute to the robustness of the cell cycle with respect to molecular noise

Most cellular oscillators rely on interlocked positive and negative regulatory feedback loops. While a negative circuit is necessary and sufficient to have limit-cycle oscillations, the role of positive feedbacks is not clear. Here we investigate the possible role of positive feedbacks in the robustness of the oscillations in presence of molecular noise. We performed stochastic simulations of a minimal 3-variable model of the cell cycle. We compare the robustness of the oscillations in the 3-variable model and in a modified model which incorporates a positive feedback loop through an auto-catalytic activation. We find that the model with a positive feedback loop is more robust to molecular noise than the model without the positive feedback loop. This increase of robustness is parameter-independent and can be explained by the attractivity properties of the limit-cycle. © 2010 Springer-Verlag Berlin Heidelberg.