Review Article | Published:

Evolutionary conservation between budding yeast and human kinetochores

Nature Reviews Molecular Cell Biology volume 2, pages 678687 (2001) | Download Citation

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Abstract

Accurate chromosome segregation during mitosis requires the correct assembly of kinetochores — complexes of centromeric DNA and proteins that link chromosomes to spindle microtubules. Studies on the kinetochore of the budding yeast Saccharomyces cerevisiae have revealed functionally novel components of the kinetochore and its regulatory complexes, some of which are highly conserved in humans.

Key points

  • The kinetochore (centromere DNA and associated proteins) and its regulating system are essential for segregating chromosomes during mitosis.

  • The kinetochore provides the site of attachment to the mitotic spindle, and is also the site at which completion of metaphase is sensed by the cell-cycle regulatory machinery to coordinate the synchronous separation of chromosomes at the onset of anaphase. The kinetochore of yeast Saccharomyces cerevisiae is the best characterized.

  • This review describes the current state of knowledge of how the kinetochore is conserved between budding yeast and humans by looking at individual kinetochore components and considers them as three sets of subcomponents: first, the chromosomal DNA–inner kinetochore protein interface; second, the inner kinetochore–mitotic spindle interface; and last, the kinetochore protein–cell-cycle regulatory machinery interface.

  • The authors conclude that molecular understanding of the less complex budding yeast kinetochore provides an excellent framework for understanding the more complex kinetochores of humans. Furthermore, evidence indicates that the kinetochore and its regulating system are indeed highly conserved between budding yeast and humans, and research into the budding yeast should continue to reveal additional conserved functions at the kinetochore.

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Affiliations

  1. Department of Molecular Pharmacology, St Jude Children's Research Hospital, 332 North Lauderdale Street, Memphis, Tennessee 38105-2794, USA.

    • Katsumi Kitagawa
  2. Biotechnology Laboratory, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3.

    • Philip Hieter
  3. Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, Canada V5Z 4H4.

    • Philip Hieter
  4. katsumi.kitagawa@stjude.org

    • Katsumi Kitagawa

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Glossary

EUPLOIDY

An entire set of chromosomes is represented in integer increments (haploid, one set; diploid, two sets; triploid, three sets).

ALPHOID DNA

α-satellite DNA; highly repetitive satellite DNA.

SCF UBIQUITIN-LIGASE COMPLEX

An E3 enzyme that targets ubiquitin to cell-cycle-regulatory proteins (for example, Sic1, Clns), using an F-box protein as a specificity factor. SCF refers to 'Skp1/Cul1/F-box protein'.

CHIP

(in vivo crosslinking chromatin-immunoprecipitation methods). After live cells are chemically crosslinked, extracted and mechanically sheared, chromatin fragments (crosslinked DNA–protein complexes) are immunoprecipitated.

BIR MOTIF

A motif found in the 'inhibition of apoptosis' (IAP) proteins. It is essential for interaction of the IAP proteins with pro-apoptotic proteins, including the caspase family of death proteases.

RING-FINGER

A cysteine-rich zinc-binding domain, which is thought to be required for protein–protein interactions.

MIDBODY

Dense structure formed during cytokinesis at the cleavage furrow. It consists of remnants of spindle fibres and other amorphous material and disappears before cell division is completed.

NOCODAZOLE

A microtubule-depolymerizing drug.

ANEUPLOIDY

One or more chromosomes of a normal set of chromosomes are missing, or present in more than their usual number of copies.

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