Accurate chromosome segregation by probabilistic self-organisation

Yasushi Saka*, Claudiu V. Giuraniuc, Hiroyuki Ohkura

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Background: For faithful chromosome segregation during cell division, correct attachments must be established between sister chromosomes and microtubules from opposite spindle poles through kinetochores (chromosome bi-orientation). Incorrect attachments of kinetochore microtubules (kMTs) lead to chromosome mis-segregation and aneuploidy, which is often associated with developmental abnormalities such as Down syndrome and diseases including cancer. The interaction between kinetochores and microtubules is highly dynamic with frequent attachments and detachments. However, it remains unclear how chromosome bi-orientation is achieved with such accuracy in such a dynamic process. Results: To gain new insight into this essential process, we have developed a simple mathematical model of kinetochore-microtubule interactions during cell division in general, i.e. both mitosis and meiosis. Firstly, the model reveals that the balance between attachment and detachment probabilities of kMTs is crucial for correct chromosome bi-orientation. With the right balance, incorrect attachments are resolved spontaneously into correct bi-oriented conformations while an imbalance leads to persistent errors. In addition, the model explains why errors are more commonly found in the first meiotic division (meiosis I) than in mitosis and how a faulty conformation can evade the spindle assembly checkpoint, which may lead to a chromosome loss. Conclusions: The proposed model, despite its simplicity, helps us understand one of the primary causes of chromosomal instability-aberrant kinetochore-microtubule interactions. The model reveals that chromosome bi-orientation is a probabilistic self-organisation, rather than a sophisticated process of error detection and correction.

Original languageEnglish
Article number65
JournalBMC Biology
Issue number1
Publication statusPublished - 12 Aug 2015

Keywords / Materials (for Non-textual outputs)

  • Chromosome segregation
  • Kinetochore
  • Markov chain
  • Meiosis
  • Microtubule
  • Mitosis
  • Self-organisation


Dive into the research topics of 'Accurate chromosome segregation by probabilistic self-organisation'. Together they form a unique fingerprint.

Cite this