Accurate chromosome segregation by probabilistic self-organisation

Yasushi Saka, Claudiu V. Giuraniuc, Hiroyuki Ohkura

Research output: Contribution to journalArticle

2 Citations (Scopus)
7 Downloads (Pure)

Abstract

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
Volume13
DOIs
Publication statusPublished - 12 Aug 2015

Fingerprint

Chromosome Segregation
chromosome segregation
self organization
Chromosomes
Kinetochores
chromosome
kinetochores
chromosomes
Microtubules
microtubules
Meiosis
Mitosis
meiosis
Cell Division
mitosis
cell division
Spindle Poles
M Phase Cell Cycle Checkpoints
Down syndrome
Conformations

Keywords

  • chromosome segregation
  • kinetochore
  • microtubule
  • mitosis
  • meiosis
  • Markov chain
  • self-organisation

Cite this

Accurate chromosome segregation by probabilistic self-organisation. / Saka, Yasushi; Giuraniuc, Claudiu V.; Ohkura, Hiroyuki.

In: BMC Biology, Vol. 13, 65, 12.08.2015.

Research output: Contribution to journalArticle

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keywords = "chromosome segregation, kinetochore, microtubule, mitosis, meiosis, Markov chain, self-organisation",
author = "Yasushi Saka and Giuraniuc, {Claudiu V.} and Hiroyuki Ohkura",
note = "We thank G Bewick, C Grebogi, S Hoppler, A Lorenz, C McCaig, F Perez-Reche, R Sekido, M Thiel and E Ullner for helpful discussions and critical reading of the manuscript. YS and CG were supported by Scottish Universities Life Sciences Alliance (SULSA) and HO by Wellcome Trust (grant numbers 098030 and 092076).",
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N2 - BackgroundFor 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.ResultsTo 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.ConclusionsThe 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.

AB - BackgroundFor 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.ResultsTo 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.ConclusionsThe 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.

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KW - meiosis

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