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kinetochore

Monday 24 November 2003

Kinetochores are large protein complexes that are formed on chromosome regions known as centromeres. For high-fidelity chromosome segregation, kinetochores must be correctly captured on the mitotic spindle before anaphase onset.

Segregation of the replicated genome during cell division in eukaryotes requires the kinetochore to link centromeric DNA to spindle microtubules.

The kinetochore is composed of a number of conserved protein complexes that direct its specification and assembly, bind to spindle microtubules and regulate chromosome segregation.

More than 80 kinetochore components have been identified. These proteins are organized into the higher order kinetochore structure, as well as how they function to achieve proper chromosome segregation.

During prometaphase, kinetochores are initially captured by a single microtubule that extends from a spindle pole and are then transported poleward along the microtubule.

Subsequently, microtubules that extend from the other spindle pole also interact with kinetochores and, eventually, each sister kinetochore attaches to microtubules that extend from opposite poles - this is known as bi-orientation.

The spindle checkpoint ensures the fidelity of chromosome segregation by preventing cell-cycle progression until all the chromosomes make proper bipolar attachments to the mitotic spindle and come under tension.

Structure

Kinetochore is a trilaminar plaque structure embedded in the chromatin at the surface of the chromosome, as visualized by electron microscopy.

At each mitosis, accurate segregation of every chromosome is ensured by the assembly of a kinetochore at each centromeric locus.

Six foundation kinetochore proteins that assemble hierarchically and co-dependently have been identified in vertebrates. CENP-A, Mis12, CENP-C, CENP-H and CENP-I localize to a core domain of centromeric chromatin. The sixth protein, CENP-B, although not essential in higher eukaryotes, has homologues in fission yeast that bind pericentric DNA and are essential for heterochromatin formation.

Foundation kinetochore proteins have various roles and mutual interactions, and their associations with centromeric DNA and heterochromatin create structural domains that support the different functions of the centromere.

Structure

The vertebrate kinetochore is a complex structure that specifies the attachments between the chromosomes and microtubules of the spindle and is thus essential for accurate chromosome segregation. Kinetochores are assembled on centromeric chromatin through complex pathways that are coordinated with the cell cycle.

See also

- mitosis
- centromeres
- kinetochore proteins (CENPs)

References

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- Amor DJ, Kalitsis P, Sumer H, Choo KH. Building the centromere: from foundation proteins to 3D organization. Trends Cell Biol. 2004 Jul;14(7):359-68. PMID: #15246429#

- Warburton PE. Epigenetic analysis of kinetochore assembly on variant human centromeres. Trends Genet. 2001 May;17(5):243-7. PMID: #11335021#