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Abstract

To ensure genome stability during mitosis, the mitotic spindle must segregate sister chromosomes accurately. Multiple surveillance mechanisms, collectively referred to as the mitotic checkpoint, function to delay anaphase onset if sister chromosomes are not bound to microtubules from opposite spindle poles. Dominant signaling pathways within the mitotic checkpoint are the Spindle Assembly Checkpoint (SAC), which delays anaphase when kinetochores are not stably attached to microtubules, and the error correction mechanism, which induces detachment when microtubule-kinetochore attachments are not under tension. Together, these mechanisms promote stable, bipolar attachments in which dynamic microtubules can generate tension across sister kinetochores. However, the interdependency of kinetochore-microtubule attachment and tension has proved challenging to understanding whether this model fully explains how the mitotic checkpoint responds to the tension status at kinetochores. Unlike higher eukaryotes, budding yeast kinetochores bind only one microtubule, simplifying the relationship between attachment and tension. To address the role of tension in the mitotic checkpoint, we developed a Taxol-sensitive yeast model to reduce tension by stabilizing microtubules in fully assembled spindles. Our results show that reducing tension on bipolar, attached kinetochores delays anaphase onset. The tension-mediated delay is transient relative to the SAC delay imposed by unattached kinetochores. Furthermore, it requires the SAC proteins Bub1 and Bub3, but persists without Mad1, Mad2 and Mad3 (yeast BubR1). Together, our results demonstrate that reduced tension generates a ‘wait-anaphase’ signal during the mitotic checkpoint that is temporally and mechanistically distinct from that of unattached kinetochores.

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