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Mechanisms of chromosome behaviour during mitosis

Nature Reviews Molecular Cell Biology volume 11, pages 91–102 (2010)Cite this article

Subjects

Key Points

  • The major goal of mitosis is to distribute the genetic material equally between two daughter cells.

  • Movement of the chromosomes on the spindle is driven by both the polymerization dynamics of microtubules and the molecular motor proteins that associate with kinetochores and chromosome arms.

  • The dynamic linkage of the microtubules to the kinetochore is probably a major factor that drives chromosome movements.

  • Chromosome congression consists of multiple individual mechanisms that enhance the fidelity of mitosis.

  • A complete understanding of the mechanisms that drive chromosome motility requires an integrated approach, combining molecular and cell biology, high-resolution imaging, biophysical and biochemical reconstitution approaches, and mathematical and computational tools.

Abstract

For over a century, scientists have strived to understand the mechanisms that govern the accurate segregation of chromosomes during mitosis. The most intriguing feature of this process, which is particularly prominent in higher eukaryotes, is the complex behaviour exhibited by the chromosomes. This behaviour is based on specific and highly regulated interactions between the chromosomes and spindle microtubules. Recent discoveries, enabled by high-resolution imaging combined with the various genetic, molecular, cell biological and chemical tools, support the idea that establishing and controlling the dynamic interaction between chromosomes and microtubules is a major factor in genomic fidelity.

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Figure 1: Structure of the mitotic spindle.
Figure 2: Organization of the kinetochore–microtubule interface.
Figure 3: Congression models for chromosome bi-orientation.
Figure 4: Congression models involving microtubule- and motor-based forces.

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Acknowledgements

The authors would like to thank all members of their laboratories for insightful discussions on chromosome motility. In particular, we are grateful to L. Weaver and J. Powers for their comments on the manuscript. Our research is supported by funding from the National Institutes of Health (GM59618 to C.E.W and GM59363 to A.K).

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Authors and Affiliations

  1. Medical Sciences Program, Indiana University, Myers Hall 262, 915 East 3rd Street, Bloomington, 47405, Indiana, USA

    Claire E. Walczak

  2. Department of Biochemistry, Indiana University, Myers Hall 262, 915 East 3rd Street, Bloomington, 47405, Indiana, USA

    Shang Cai

  3. Division of Translational Medicine, New York State Department of Health, Wadsworth Center, Albany, 12201, New York, USA

    Alexey Khodjakov

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  1. Claire E. Walczak
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Correspondence to Claire E. Walczak or Alexey Khodjakov.

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Glossary

Centromere

A specialized thin region, often referred to as the 'primary constriction', on a chromosome. It is composed of highly condensed heterochromatin that serves as the platform for the assembly of kinetochores.

Kinetochore

A structure that assembles on the mitotic chromosome to attach to microtubules of the spindle.

K-fibre

A bundle of microtubules that connects to a kinetochore on a mitotic chromosome.

Segregation

The process by which sister chromatids are distributed to two daughter cells.

Spindle assembly checkpoint

A surveillance mechanism that monitors the attachment state of individual chromosomes. The checkpoint blocks anaphase onset until the kinetochores are attached to microtubules of the spindle.

Centrosome

A specialized organelle at the spindle pole that is the site of microtubule nucleation.

Congression

The process by which chromosomes align at the spindle equator.

Bi-oriented

Here, used to describe the attachment of a chromosome to microtubules emanating from opposite spindle poles.

Centromeric heterochromatin

Distinct regions of chromatin at the centromere of a chromosome that are highly condensed and contribute to specifying the location of kinetochore assembly.

Astral microtubule

A microtubule that emanates from the spindle pole to the cell cortex.

Mono-oriented

Here, used to describe the attachment of a chromosome to microtubules coming from a single spindle pole.

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Walczak, C., Cai, S. & Khodjakov, A. Mechanisms of chromosome behaviour during mitosis. Nat Rev Mol Cell Biol 11, 91–102 (2010). https://doi.org/10.1038/nrm2832

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