Kinetochore: Structure, Function and Evolution

Kinetochores are complexes of centromere DNA and proteins. Spindle microtubules bind to chromosomes at the kinetochore, and these complexes are required for accurate chromosome segregation during mitosis. The human kinetochore is a supramolecular complex of DNA and proteins that is involved in various mitotic activities.

Keywords: kinetochore; centromere; mitosis; chromosome segregation; spindle checkpoint

Figure 1. Human kinetochore ultrastructure. The box on the left shows proteins whose locations in the ultrastructure have not been determined by immunoelectron microscopy. Note that MCAK may be located in the inner plate and/or the interzone, as well as in the heterochromatin domain. In addition, three‐dimensional deconvolution studies have shown that CENPA and CENPC are juxtaposed and that CENPA is predominantly located beneath the kinetochore.
Figure 2. Solenoid model of the centromeric chromatin domain. Blocks of CENPA (open spheres) and H3 nucleosomes (filled spheres) are arranged in a solenoid. During metaphase, CENPA nucleosomes are present on the poleward side of the chromosome, and H3 nucleosomes are located between the paired sister kinetochores. Alternatively, in the looping model (not shown), centromeric DNA might loop, rather than spiral, through the elliptical structure.
Figure 3. Role of the kinetochore in progression of anaphase. The spindle checkpoint delays mitosis (open arrow) in response to kinetochores that are improperly attached to microtubules (spheres). This delay occurs when components of the spindle checkpoint are recruited to the kinetochore. These components inhibit the anaphase‐promoting complex (APC) and thus delay mitosis. CDC20 is a specificity factor that activates the APC; the activated complex then binds to securin and allows the ubiquitination of the substrate. Securin inhibits the protease activity of separase. The APC targets securin and destroys it, thereby allowing separase to cleave the cohesin (boxes) that holds the sister chromatids together. This cleavage triggers anaphase.
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 Further Reading
    Choo KH (2001) Domain organization at the centromere and neocentromere. Developmental Cell 1: 165–177.
    Henikoff S, Ahmad K and Malik HS (2001) The centromere paradox: stable inheritance with rapidly evolving DNA. Science 293: 1098–1102.
    Hoyt MA (2001) A new view of the spindle checkpoint. Journal of Cell Biology 154: 909–911.
    Jallepalli PV and Lengauer C (2001) Chromosome segregation and cancer: cutting through the mystery. Nature Reviews Cancer 1: 109–117.
    Kitagawa K and Hieter P (2001) Evolutionary conservation between budding yeast and human kinetochores. Nature Reviews Molecular Cell Biology 2: 678–687.
    Maney T, Ginkel LM, Hunter AW and Wordeman L (2000) The kinetochore of higher eucaryotes: a molecular view. International Review of Cytology 194: 67–131.
    Nasmyth K (2001) Disseminating the genome: joining, resolving, and separating sister chromatids during mitosis and meiosis. Annual Reviews in Genetics 35: 673–745.
    Pidoux AL and Allshire RC (2000) Centromeres: getting a grip of chromosomes. Current Opinion in Cell Biology 12: 308–319.
    book Rieder CL (ed.) (1998) Mitosis and Meiosis. Methods in Cell Biology,vol. 61. San Diego, CA: Academic Press.
    Rieder CL and Salmon ED (1998) The vertebrate cell kinetochore and its roles during mitosis. Trends in Cell Biology 8: 310–318.
    Skibbens RV and Hieter P (1998) Kinetochores and the checkpoint mechanism that monitors for defects in the chromosome segregation machinery. Annual Reviews in Genetics 32: 307–337.
    Sullivan BA, Blower MD and Karpen GH (2001) Determining centromere identity: cyclical stories and forking paths. Nature Reviews Genetics 2: 584–596.
    Tyler‐Smith C and Floridia G (2000) Many paths to the top of the mountain: diverse evolutionary solutions to centromere structure. Cell 102: 5–8.
    Wassmann K and Benezra R (2001) Mitotic checkpoints: from yeast to cancer. Current Opinion in Genetics and Development 11: 83–90.
 Web Links
    ePath BUB1 budding uninhibited by benzimidazoles 1 homolog beta (BUB1B); LocusID: 701. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=701
    ePath BUB1 budding uninhibited by benzimidazoles 1 homolog (BUB1); LocusID: 699. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=699
    ePath Centromere protein A, 17 kDa (CENPA); LocusID: 1058. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=1058
    ePath Centromere protein B, 80 kDa (CENPB); LocusID: 1059. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=1059
    ePath ZW10 homolog, centromere/kinetochore protein (ZW10); LocusID: 9183. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=9183
    ePath BUB1 budding uninhibited by benzimidazoles 1 homolog (BUB1); MIM number: 602452. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?602452
    ePath BUB1 budding uninhibited by benzimidazoles 1 homolog beta (BUB1B); MIM number: 602860. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?602860
    ePath Centromere protein A, 17 kDa (CENPA); MIM number: 117139. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?117139
    ePath Centromere protein B, 80 kDa (CENPB); MIM number: 117140. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?117140
    ePath ZW10 homolog, centromere/kinetochore protein (ZW10); MIM number: 9183. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?9183
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How to Cite close
Kitagawa, Katsumi(Sep 2006) Kinetochore: Structure, Function and Evolution. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0006237]