A Regulatory Switch Alters Chromosome Motions at the Metaphase-to-Anaphase Transition.
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 chromosome dynamics 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.
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.
Kuan-Chung
KC
Su
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Zachary
Z
Barry
Chromosome Instability and Dynamics Laboratory, Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135 Porto, Portugal; i3S - Instituto de Investigação e Inovação em Saúdem, Universidade do Porto, 4200-135 Porto, Portugal.
Nina
N
Schweizer
Chromosome Instability and Dynamics Laboratory, Instituto de Biologia Molecular e Celular, Universidade do Porto, 4200-135 Porto, Portugal; i3S - Instituto de Investigação e Inovação em Saúdem, Universidade do Porto, 4200-135 Porto, Portugal; Cell Division Unit, Department of Experimental Biology, Faculdade de Medicina, Universidade do Porto, 4200-135 Porto, Portugal.
Helder
H
Maiato
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Mark
M
Bathe
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA. Electronic address: icheese@wi.mit.edu.
Iain McPherson
IM
Cheeseman
D000705:Anaphase / Q000187:drug effects; D002842:Chromatids / Q000378:metabolism; D002877:Chromosomes, Human / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000187:drug effects / Q000378:metabolism; D008677:Metaphase / Q000187:drug effects; D008954:Models, Biological; D009068:Movement; D019319:Okadaic Acid / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects
D019319:Okadaic Acid
chromokinesin; kinetochore; microtubule; mitosis; phosphorylation