Computer simulations predict that chromosome movements and rotations accelerate mitotic spindle assembly without compromising accuracy

Raja Paul, Roy Wollman, William T. Silkworth, Isaac K. Nardi, Daniela Cimini, Alex Mogilner

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

The mitotic spindle self-assembles in prometaphase by a combination of centrosomal pathway, in which dynamically unstable microtubules search in space until chromosomes are captured, and a chromosomal pathway, in which microtubules grow from chromosomes and focus to the spindle poles. Quantitative mechanistic understanding of how spindle assembly can be both fast and accurate is lacking. Specifically, it is unclear how, if at all, chromosome movements and combining the centrosomal and chromosomal pathways affect the assembly speed and accuracy. We used computer simulations and high-resolution microscopy to test plausible pathways of spindle assembly in realistic geometry. Our results suggest that an optimal combination of centrosomal and chromosomal pathways, spatially biased microtubule growth, and chromosome movements and rotations is needed to complete prometaphase in 10-20 min while keeping erroneous merotelic attachmentsdownto a few percent. The simulations also provide kinetic constraints for alternative error correction mechanisms, shed light on the dual role of chromosome arm volume, and compare well with experimental data for bipolar and multipolar HT-29 colorectal cancer cells.

Original languageEnglish (US)
Pages (from-to)15708-15713
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number37
DOIs
StatePublished - Sep 15 2009

Keywords

  • Assembly speed and accuracy
  • Merotelic attachments
  • Microtubules
  • Search and capture

ASJC Scopus subject areas

  • General

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