Centromeres

Abstract

The centromere is a eukaryotic chromosomal substructure that ensures the accurate segregation of newly replicated chromosomes to daughter cells. It carries out this essential cell cycle process via multiple functions such as, spindle microtubule attachment, mitotic checkpoint control, sister‐chromatid cohesion and release and cytokinesis. This article explores the structure and function of the centromere in many well‐studied eukaryotic organisms.

Keywords: kinetochore; chromosome; artificial centromere; artificial chromosome; epigenetic regulation; heterochromatin; chromatin

Figure 1.

Centromere DNA of different organisms. (a) Saccharomyces cerevisiae, showing DNA elements CDEI, II and III. (b) Schizosaccharomyces pombe, showing the nonrepetitive central core (cc) and various inverted repeats, including the functionally critical K‐type repeats. (c) Parascaris univalens, showing the three different centromere states in which kinetochores are formed: along the entire length of the chromosome (state 1); only at the tips of the chromosome (state 2) or only in the middle euchromatic DNA before (state 3a) and after (state 3b) heterochromatin elimination and chromosome diminution. (d) Drosophila melanogaster, showing the distribution of simple repeats, transposable elements and nonrepetitive DNA within the centromere of the Dp1187 minichromosome. (e) Humans, showing α‐satellite DNA on a normal centromere (above) and non‐α‐satellite genomic DNA on a neocentromere (below).

Figure 2.

Organization of Sa. cerevisiae centromere–kinetochore complex, showing the centromere DNA‐associated complexes centred around the Cse4p:H4:SCM3 nucleosome, followed by the linker and microtubule (MT)‐associated proteins. For simplicity, individual protein components are not shown in some of the complexes. Reproduced with permission from Westermann S et al. () Structures and Functions of Yeast Kinetochore Complexes. Annual Review of Biochemistry: March 15.

Figure 3.

Structural and functional domains of a mammalian centromere.

Figure 4.

Known examples of different chromosomal rearrangements causing neocentromere formation. (a) An inverted duplication on the short arm of chromosome 20 results in an inv dup(20) chromosome carrying a neocentromere on band p12 on one of the two duplicated segments. (b) An interstitial deletion on the short arm p32→p36.1 region of chromosome 1 results in a neocentromere‐containing ring chromosome rder(1). (c) A fusion between a short‐arm and a long‐arm terminal segment of chromosome 10 results in the formation of mardel(10) with a neocentromere at band q25.

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References

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Further Reading

Alberts B, Johnson A, Lewis J et al. (2002) Molecular Biology of the Cell, 4th edn. New York: Garland Publishing.

Amor DJ and Choo KHA (2002) Neocentromeres: role in human disease, evolution, and centromere study. American Journal of Human Genetics 71: 695–714.

Amor DJ, Kalitsis P, Sumer H and Choo KHA (2004) Building the centromere: from foundation proteins to 3D organization. Trends in Cell Biology 14: 359–368.

Choo KHA (1997) The Centromere. Oxford: Oxford University Press.

Irvine DV, Shaw ML, Choo KHA and Saffery R (2005) Engineering chromosomes for delivery of therapeutic genes. Trends in Biotechnology 23: 575–583.

Kops GJPL, Weaver BAA and Cleveland DW (2005) On the road to cancer: aneuploidy and the mitotic checkpoint. Nature Reviews. Cancer 5: 773–785.

Meraldi P, McAinsh AD, Rheinbay E and Sorger PK (2006) Phylogenetic and structural analysis of centromeric DNA and kinetochore proteins. Genome Biology 7: R23.

Rieder CL and Maiato H (2004) Stuck in division or passing through: what happens when cells cannot satisfy the spindle assembly checkpoint. Developmental Cell 7: 637–651.

Webgraphy

Edward D. Salmon's lab page – Mitosis, kinetochores and live cell imaging www.bio.unc.edu/faculty/salmon/lab/

Kerry Bloom's Lab – Budding yeast centromere www.bio.unc.edu/bloom/lab

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How to Cite close
Kalitsis, Paul(Jul 2008) Centromeres. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001166.pub2]