Role of the Number of Microtubules in Chromosome Segregation during Cell Division

PLoS One. 2015 Oct 27;10(10):e0141305. doi: 10.1371/journal.pone.0141305. eCollection 2015.

Abstract

Faithful segregation of genetic material during cell division requires alignment of chromosomes between two spindle poles and attachment of their kinetochores to each of the poles. Failure of these complex dynamical processes leads to chromosomal instability (CIN), a characteristic feature of several diseases including cancer. While a multitude of biological factors regulating chromosome congression and bi-orientation have been identified, it is still unclear how they are integrated so that coherent chromosome motion emerges from a large collection of random and deterministic processes. Here we address this issue by a three dimensional computational model of motor-driven chromosome congression and bi-orientation during mitosis. Our model reveals that successful cell division requires control of the total number of microtubules: if this number is too small bi-orientation fails, while if it is too large not all the chromosomes are able to congress. The optimal number of microtubules predicted by our model compares well with early observations in mammalian cell spindles. Our results shed new light on the origin of several pathological conditions related to chromosomal instability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / genetics
  • Chromosomal Instability / genetics*
  • Chromosome Disorders / genetics
  • Chromosome Disorders / pathology
  • Chromosome Segregation / genetics*
  • Dyneins / genetics*
  • Dyneins / metabolism
  • Humans
  • Microtubules / genetics*
  • Mitosis / genetics
  • Spindle Apparatus / genetics

Substances

  • Dyneins

Grants and funding

Z. Bertalan, Z. Budrikis, and SZ are supported by the European Research Council Advanced Grant 291002 SIZEFFECTS. CAMLP thanks the visiting professor program of Aalto University where part of this work was completed. SZ acknowledges support from the Academy of Finland FiDiPro program, project 13282993. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.