A Regulatory Switch Alters Chromosome Motions at the Metaphase-to-Anaphase Transition
Author(s)Su, Kuan-Chung; Schweizer, Nina; Maiato, Helder; Bathe, Mark; Barry, Zachary Thomas; Cheeseman, Iain M; ... Show more Show less
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To achieve chromosome segregation during mitosis, sister chromatids must undergo a dramatic change in their behavior to switch from balanced oscillations at the metaphase plate to directed poleward motion during anaphase. However, the factors that alter chromosome behavior at the metaphase-to-anaphase transition remain incompletely understood. Here, we perform time-lapse imaging to analyze anaphase chromosomedynamics in human cells. Using multiple directed biochemical, genetic, and physical perturbations, our results demonstrate that differences in the global phosphorylation states between metaphase and anaphase are the major determinant of chromosome motion dynamics. Indeed, causing a mitotic phosphorylation state to persist into anaphase produces dramatic metaphase-like oscillations. These induced oscillations depend on both kinetochore-derived and polar ejection forces that oppose poleward motion. Thus, our analysis of anaphase chromosome motion reveals that dephosphorylation of multiple mitotic substrates is required to suppress metaphase chromosome oscillatory motions and achieve directed poleward motion for successful chromosome segregation.
DepartmentMassachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Biology
Su, Kuan-Chung, Zachary Barry, Nina Schweizer, Helder Maiato, Mark Bathe, and Iain McPherson Cheeseman. “A Regulatory Switch Alters Chromosome Motions at the Metaphase-to-Anaphase Transition.” Cell Reports 17, no. 7 (November 2016): 1728–1738.
Final published version