Figure 5.

The mammalian kinetochore integrates attachment input signals in a sensitive and switch-like manner. Microtubules bind kinetochore attachment subunits independently rather than cooperatively, leading to a wide range of kinetochore–microtubule attachment numbers (left; Fig. 1). The speed of this response, the loss of Mad1, is sensitive to the number of microtubules attached (middle): Mad1 loss rates are slow at weakly attached kinetochores (Fig. 3) and reach a maximum at kinetochores with WT attachment numbers (Kuhn and Dumont, 2017). However, kinetochores with very low microtubule occupancy are still capable of fully removing Mad1 (Fig. 2), resulting in a decision-making process that is highly sensitive and switch-like (right). The combination of switch-like decision making and a tunable response rate is well suited to allow cells to rapidly exit mitosis while preventing errors (see Discussion).