Robust microtubule dynamics facilitate low-tension kinetochore detachment in metaphase

强大的微管动力学促进中期低张力动粒分离

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作者:Sneha Parmar, Samuel J Gonzalez, Julia M Heckel, Soumya Mukherjee, Mark McClellan, Duncan J Clarke, Marnie Johansson, Damien Tank, Athena Geisness, David K Wood, Melissa K Gardner

Abstract

During mitosis, sister chromatids are stretched apart at their centromeres via their attachment to oppositely oriented kinetochore microtubules. This stretching generates inwardly directed tension across the separated sister centromeres. The cell leverages this tension signal to detect and then correct potential errors in chromosome segregation, via a mechanical tension signaling pathway that detaches improperly attached kinetochores from their microtubules. However, the sequence of events leading up to these detachment events remains unknown. In this study, we used microfluidics to sustain and observe low-tension budding yeast metaphase spindles over multiple hours, allowing us to elucidate the tension history prior to a detachment event. We found that, under conditions in which kinetochore phosphorylation weakens low-tension kinetochore-microtubule connections, the mechanical forces produced via the dynamic growth and shortening of microtubules is required to efficiently facilitate detachment events. Our findings underscore the critical role of robust kinetochore microtubule dynamics in ensuring the fidelity of chromosome segregation during mitosis.

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