A Gradient in Metaphase Tension Leads to a Scaled Cellular Response in Mitosis

Soumya Mukherjee, Brian J Sandri, Damien Tank, Mark McClellan, Lauren A. Harasymiw, Qing Yang, Laurie L Parker, Melissa K Gardner

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

During mitosis, motor proteins associate with microtubules to exert pushing forces that establish a mitotic spindle. These pushing forces generate opposing tension in the chromatin that connects oppositely attached sister chromatids, which may then act as a mechanical signal to ensure the fidelity of chromosome segregation during mitosis. However, the role of tension in mitotic cellular signaling remains controversial. In this study, we generated a gradient in tension over multiple isogenic budding yeast cell lines by genetically altering the magnitude of motor-based spindle forces. We found that a decreasing gradient in tension led to an increasing gradient in the rates of kinetochore detachment and anaphase chromosome mis-segregration, and in metaphase time. Simulations and experiments indicated that these tension responses originate from a tension-dependent kinetochore phosphorylation gradient. We conclude that the cell is exquisitely tuned to the magnitude of tension as a signal to detect potential chromosome segregation errors during mitosis. Mukherjee et al. demonstrate that cells are able to detect the magnitude of the tension that is built up across the centromeric regions of chromosomes at metaphase, and that cells respond to these changes to prevent chromosome mis-segregation in mitosis. Tension sensing thus underlies a fundamental mechanochemical mitotic safety mechanism.

Original languageEnglish (US)
Pages (from-to)63-76.e10
JournalDevelopmental Cell
Volume49
Issue number1
DOIs
StatePublished - Apr 8 2019

Fingerprint

Metaphase
Chromosomes
Mitosis
Chromosome Segregation
Kinetochores
Anaphase
Spindle Apparatus
Saccharomycetales
Chromatids
Cell signaling
Phosphorylation
Microtubules
Chromatin
Yeast
Safety
Cell Line
Cells
Proteins
Experiments

Keywords

  • Dam1
  • centromere
  • checkpoint
  • chromosome
  • kinetochore
  • metaphase
  • mitosis
  • tension
  • yeast

PubMed: MeSH publication types

  • Journal Article

Cite this

A Gradient in Metaphase Tension Leads to a Scaled Cellular Response in Mitosis. / Mukherjee, Soumya; Sandri, Brian J; Tank, Damien; McClellan, Mark; Harasymiw, Lauren A.; Yang, Qing; Parker, Laurie L; Gardner, Melissa K.

In: Developmental Cell, Vol. 49, No. 1, 08.04.2019, p. 63-76.e10.

Research output: Contribution to journalArticle

Mukherjee, Soumya ; Sandri, Brian J ; Tank, Damien ; McClellan, Mark ; Harasymiw, Lauren A. ; Yang, Qing ; Parker, Laurie L ; Gardner, Melissa K. / A Gradient in Metaphase Tension Leads to a Scaled Cellular Response in Mitosis. In: Developmental Cell. 2019 ; Vol. 49, No. 1. pp. 63-76.e10.
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