The spatial arrangement of chromosomes during prometaphase facilitates spindle assembly

Valentin Magidson, Christopher B. O'Connell, Jadranka Lončarek, Raja Paul, Alex Mogilner, Alexey Khodjakov

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)555-567
Number of pages13
JournalCell
Volume146
Issue number4
DOIs
StatePublished - Aug 19 2011

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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