The Spatial Arrangement of Chromosomes during Prometaphase Facilitates Spindle Assembly

Error-free chromosome segregation requires stable attachment of sister kinetochores to the opposite spindle poles (amphitelic attachment). Exactly how amphitelic attachments are achieved during spindle assembly remains elusive. We employed photoactivatable GFP and high-resolution live-cell confocal...

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Bibliographic Details
Published in:Cell 2011-08, Vol.146 (4), p.555-567
Main Authors: Magidson, Valentin, O'Connell, Christopher B., Lončarek, Jadranka, Paul, Raja, Mogilner, Alex, Khodjakov, Alexey
Format: Article
Language:English
Subjects:
Animals
Cell Line
Centromere - metabolism
Chromosomes
Chromosomes - metabolism
Confocal microscopy
Data processing
Electron microscopy
Humans
Immunofluorescence
Kinetochores
Kinetochores - metabolism
Mathematical models
Mice
Microtubules
Microtubules - metabolism
Mitosis
Models, Molecular
Prometaphase
Spindle Apparatus - metabolism
Spindles
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Summary:Error-free chromosome segregation requires stable attachment of sister kinetochores to the opposite spindle poles (amphitelic attachment). Exactly how amphitelic attachments are achieved during spindle assembly remains elusive. We employed photoactivatable GFP and high-resolution live-cell confocal microscopy to visualize complete 3D movements of individual kinetochores throughout mitosis in nontransformed human cells. Combined with electron microscopy, molecular perturbations, and immunofluorescence analyses, this approach reveals unexpected details of chromosome behavior. Our data demonstrate that unstable lateral interactions between kinetochores and microtubules dominate during early prometaphase. These transient interactions lead to the reproducible arrangement of chromosomes in an equatorial ring on the surface of the nascent spindle. A computational model predicts that this toroidal distribution of chromosomes exposes kinetochores to a high density of microtubules which facilitates subsequent formation of amphitelic attachments. Thus, spindle formation involves a previously overlooked stage of chromosome prepositioning which promotes formation of amphitelic attachments. [Display omitted] ► In human cells, chromosomes form a ring around the spindle during prometaphase ► This arrangement requires chromokinesin-mediated ejection of chromosome arms ► Formation of the ring accelerates spindle assembly ► Stable amphitelic attachments form during late prometaphase and metaphase
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2011.07.012