Low tension recruits the yeast Aurora B protein Ipl1 to centromeres in metaphase

Abstract

Accurate genome segregation in mitosis requires that all chromosomes are bioriented on the spindle. Cells monitor biorientation by sensing tension across sister centromeres. Chromosomes that are not bioriented have low centromere tension, which allows Aurora B (yeast Ipl1) to perform error correction that locally loosens kinetochore-microtubule attachments to allow detachment of microtubules and fresh attempts at achieving biorientation. However, it is not known if low tension recruits Aurora B to centromeres or, alternatively, if low tension directly activates Aurora B already localized at centromeres. In this work, we experimentally induced low tension in metaphase yeast cells, then monitored Ipl1 localization. We find low tension recruits Ipl1 to centromeres. Further, low tension induced Ipl1 recruitment depended on Bub1, which is known to provide a binding site for Ipl1. In contrast, Top2, which can also recruit Ipl1 to centromeres, was not required. Our results demonstrate cells are sensitive to low tension at centromeres and respond by actively recruiting Ip1l for error correction.

Kinetochore–microtubule error correction for biorientation: lessons from yeast

“…However, using an engineered recruitment of Aurora B–INCENP, it was suggested that this turnover is not required for error correction [ 88 ]. Another report indicated that the level of CPC at the kinetochore/centromere is reduced a while after the establishment of the bipolar spindle [ 89 ]. This may not regulate error correction in an unperturbed cell cycle since biorientation is rapidly established following the bipolar spindle formation [ 47 , 90 ], but may contribute to the maintenance of biorientation when metaphase is extended.…”

Spindle architecture constrains karyotype in budding yeast

“…To test this hypothesis, we reduced the amount of outward force by treating the cells with a low concentration of benomyl. Benomyl is a tubulin-binding drug, which at low concentrations can decrease metaphase spindle length by suppressing microtubule dynamics without inducing detachments ( 19, 20 ). Treatment with benomyl did indeed fix both the growth and mitotic defect (Fig.…”

“…In wild-type cells, perturbations that reduce outward forces in the metaphase spindle, like treatment with benomyl or KIP1 deletion, were shown to increase the rate of kinetochore detachments and increase metaphase duration due to reduced tension at the kinetochores ( 20, 21 ). Low tension is a signal for improper biorientation, and leads to microtubule detachment through activation of the Aurora B-dependent error correction mechanism ( 22 ).…”