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.
Bibliographical noteFunding Information:
M.K.G. is supported by a National Institutes of Health grant NIGMS GM-103833 and National Science Foundation CAREER award 1350741. We would like to thank Drs. Trisha Davis, Sue Biggins, Tomoyuki Tanaka, David O. Morgan, and Duncan Clarke for generous gifts of strains and constructs. The University of Minnesota Center for Mass Spectrometry (CMSP) helped develop the quantitative MRM method, especially Bruce Witthuhn. We thank Drs. Duncan Clarke, Heather Edgerton, Trisha Davis, and the Gardner Laboratory, in particular, Dr. Jeremy Chacon, for helpful discussions.
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