Robust microtubule dynamics facilitate low-tension kinetochore detachment in metaphase

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

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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 kinetochoremicrotubule 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.

Original languageEnglish (US)
Article numbere202202085
JournalJournal of Cell Biology
Volume222
Issue number8
DOIs
StatePublished - Aug 7 2023

Bibliographical note

Publisher Copyright:
© 2023 Parmar et al.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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