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Abstract

Major transitions from one cell cycle phase to the next are implemented with positive feedback loops in their regulatory pathways, which ensures that they occur quickly and are irreversible. The transition from metaphase to anaphase is visually one of the most dramatic transitions in the cell cycle. Since chromosomes split abruptly and synchronously, it is natural to assume that this transition involves positive feedback, and some evidence has been found in budding yeast. We now show that chromosome splitting can be slowed down and made more asynchronous by several different perturbations in fission yeast. We find a tendential order in the time when different chromosomes separate, which is aggravated when slowing down separation. Because affecting different steps in the segregation pathway all lead to a less abrupt separation, we conclude that feedback happens, if at all, far upstream, but not at the level of the direct regulators. Hence, sister chromatid separation, being already irreversible by nature, may be one of the few major cell cycle transitions that can operate without positive feedback.