Abstract
The centromere is the genetic locus required for chromosome segregation. It is the site of spindle attachment to the chromosomes and is crucial for the transfer of genetic information between cell and organismal generations. Although the centromere was first recognized more than 120 years ago, little is known about what determines its site(s) of activity, and how it contributes to kinetochore formation and spindle attachment. Recent work in this field has supported the hypothesis that most eukaryotic centromeres are determined epigenetically rather than by primary DNA sequence. Here, we review recent studies that have elucidated the organization and functions of centromeric chromatin, and evaluate present-day models for how centromere identity and propagation are determined.
Key Points
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Eukaryotic centromeres are encoded by non-conserved DNAs but contain highly conserved proteins, such as CENPA. Furthermore, centromeric DNAs that lack centromere function and non-centromeric DNAs can gain centromere function. Despite a lack of conservation in centromeric DNA sequence, (A+T)-rich or repetitive DNA might be a primary substrate for kinetochore assembly.
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CENPA is an essential kinetochore histone that might epigenetically mark sites for kinetochore formation and is required for the proper localization of kinetochore and sister-chromatid cohesion proteins. It is also required for mitotic and cell-cycle progression. Its incorporation into centromeres is independent of:
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centromeric DNA replication, because replication studies of human and Drosophila centromeres indicate that centromeric DNAs are replicated asynchronously in S phase, and in humans are replicated before CENPA is loaded onto chromatin;
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the spatial organization or sequestration of centromeres or replication domains.
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Eukaryotic centromere regions are composed of several spatial and functional domains.
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Epigenetic propagation of centromere identity might be achieved through the activity of centromere-specific chromatin-assembly factors, which load CENPA into centromeric nucleosomes.
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Despite recent advances in our understanding of centromere function, many mechanistic details remain to be understood.
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References
Borges, J. L. in Jorge Luis Borges: Collected Fictions 125 (Penguin Books, New York City, 1998).An example of metafiction dealing with cycles of life, written by a master of the genre.
Hassold, T. & Hunt, P. To err (meiotically) is human: the genesis of human aneuploidy. Nature Rev. Genet. 2, 280–291 (2001).
Mitelman, F. Catalog of Chromosome Aberrations in Cancer (Wiley, New York, 1994).
Flemming, W. Beitrag zur Kenntnis der Zelle und ihrer Lebenserscheinungen, Teil II. Archiv. Mikrosk. Anat. 18, 151–259 (1880).The first clear cytological description of the centromere.
Rieder, C. L. & Salmon, E. D. The vertebrate cell kinetochore and its roles during mitosis. Trends Cell Biol. 8, 310–318 (1998).
Shah, J. V. & Cleveland, D. W. Waiting for anaphase: Mad2 and the spindle assembly checkpoint. Cell 103, 997–1000 (2000).
Cahill, D. P. et al. Mutations of mitotic checkpoint genes in human cancers. Nature 392, 300–303 (1998).
Dej, K. J. & Orr-Weaver, T. L. Separation anxiety at the centromere. Trends Cell Biol. 10, 392–399 (2000).
Toth, A. et al. Functional genomics identifies monopolin: a kinetochore protein required for segregation of homologs during meiosis I. Cell 103, 1155–1168 (2000).
White, M. J. D. Animal Cytology and Evolution (Cambridge Univ. Press, Cambridge, UK, 1973).
Pimpinelli, S. & Goday, C. Unusual kinetochores and chromatin diminution in Parascaris. Trends Genet. 5, 310–315 (1989).
Sullivan, K. F. A solid foundation: functional specialization of centromeric chromatin. Curr. Opin. Genet. Dev. 11, 182–188 (2001).
Karpen, G. H. & Allshire, R. C. The case for epigenetic effects on centromere identity and function. Trends Genet. 13, 489–496 (1997).
Hyman, A. A. & Sorger, P. K. Structure and function of kinetochores in budding yeast. Annu. Rev. Cell Dev. Biol. 11, 471–495 (1995).
Weiler, K. S. & Wakimoto, B. T. Heterochromatin and gene expression in Drosophila. Annu. Rev. Genet. 29, 577–605 (1995).
Clarke, L., Amstutz, H., Fishel, B. & Carbon, J. Analysis of centromeric DNA in the fission yeast Schizosaccharomyces pombe. Proc. Natl Acad. Sci. USA 83, 8253–8257 (1986).
Nakaseko, Y., Adachi, Y., Funahashi, S., Niwa, O. & Yanagida, M. Chromosome walking shows a highly repetitive sequence present in all the centromere regions of fission yeast. EMBO J. 5, 1011–1021 (1986).
Nakaseko, Y., Kinoshita, N. & Yanagida, M. A novel sequence common to the centromere regions of Schizosaccharomyces pombe chromosomes. Nucleic Acids Res. 15, 4705–4715 (1987).
Baum, M., Ngan, V. K. & Clarke, L. The centromeric K-type repeat and the central core are together sufficient to establish a functional Schizosaccharomyces pombe centromere. Mol. Biol. Cell 5, 747–761 (1994).
Hahnenberger, K. M., Carbon, J. & Clarke, L. Identification of DNA regions required for mitotic and meiotic functions within the centromere of Schizosaccharomyces pombe chromosome I. Mol. Cell. Biol. 11, 2206–2215 (1991).
Murakami, S., Matsumoto, T., Niwa, O. & Yanagida, M. Structure of the fission yeast centromere cen3: direct analysis of the reiterated inverted region. Chromosoma 101, 214–221 (1991).
Allshire, R. C., Nimmo, E. R., Ekwall, K., Javerzat, J. P. & Cranston, G. Mutations derepressing silent centromeric domains in fission yeast disrupt chromosome segregation. Genes Dev. 9, 218–233 (1995).
Partridge, J. F., Borgstrom, B. & Allshire, R. C. Distinct protein interaction domains and protein spreading in a complex centromere. Genes Dev. 14, 783–791 (2000).By analysing chromatin content, this study showed that the Schizosaccharomyces pombe centromere is composed of spatially and functionally separate protein domains.
Murphy, T. D. & Karpen, G. H. Localization of centromere function in a Drosophila minichromosome. Cell 82, 599–609 (1995).
Sun, X., Wahlstrom, J. & Karpen, G. Molecular structure of a functional Drosophila centromere. Cell 91, 1007–1019 (1997).References 24 and 25 report the first genetic and molecular definition of a functional centromere in a metazoan.
Willard, H. F. Centromeres: the missing link in the development of human artificial chromosomes. Curr. Opin. Genet. Dev. 8, 219–225 (1998).
Warburton, P. E. et al. Immunolocalization of CENP-A suggests a distinct nucleosome structure at the inner kinetochore plate of active centromeres. Curr. Biol. 7, 901–904 (1997).
Mills, W., Critcher, R., Lee, C. & Farr, C. J. Generation of an approximately 2.4 Mb human X centromere-based minichromosome by targeted telomere-associated chromosome fragmentation in DT40. Hum. Mol. Genet. 8, 751–761 (1999).
Wevrick, R., Earnshaw, W. C., Howard-Peebles, P. N. & Willard, H. F. Partial deletion of alpha satellite DNA associated with reduced amounts of the centromere protein CENP-B in a mitotically stable human chromosome rearrangement. Mol. Cell. Biol. 10, 6374–6380 (1990).
Yang, J. W. et al. Human mini-chromosomes with minimal centromeres. Hum. Mol. Genet. 9, 1891–1902 (2000).
Harrington, J. J., Van Bokkelen, G., Mays, R. W., Gustashaw, K. & Willard, H. F. Formation of de novo centromeres and construction of first-generation human artificial microchromosomes. Nature Genet. 15, 345–355 (1997).
Ikeno, M. et al. Construction of YAC-based mammalian artificial chromosomes. Nature Biotechnol. 16, 431–439 (1998).References 31 and 32 are landmark papers that describe the construction and mitotic stablility of human artificial chromosomes using synthetic (31) or cloned (32) alpha satellite arrays to seed kinetochore formation in tissue culture cells.
Murata, M., Ogura, Y. & Motoyoshi, F. Centromeric repetitive sequences in Arabidopsis thaliana. Jpn. J. Genet. 69, 361–370 (1994).
Round, E. K., Flowers, S. K. & Richards, E. J. Arabidopsis thaliana centromere regions: genetic map positions and repetitive DNA structure. Genome Res. 7, 1045–1053 (1997).
Copenhaver, G. P. et al. Genetic definition and sequence analysis of Arabidopsis centromeres. Science 286, 2468–2474 (1999).
Heslop-Harrison, J. S., Murata, M., Ogura, Y., Schwarzacher, T. & Motoyoshi, F. Polymorphisms and genomic organization of repetitive DNA from centromeric regions of Arabidopsis chromosomes. Plant Cell 11, 31–42 (1999).
Merriam, J. R. & Frost, J. N. Exchange and nondisjunction of the X chromosomes in female Drosophila melanogaster. Genetics 49, 109–122 (1964).
Szauter, P. An analysis of regional constraints on exchange in Drosophila melanogaster using recombination-defective meiotic mutants. Genetics 106, 45–71 (1984).
Gindullis, F., Desel, C., Galasso, I. & Schmidt, T. The large-scale organization of the centromeric region in beta species. Genome Res. 11, 253–265 (2001).
Stinchcomb, D. T., Shaw, J. E., Carr, S. H. & Hirsh, D. Extrachromosomal DNA transformation of Caenorhabditis elegans. Mol. Cell. Biol. 5, 3484–3496 (1985).
Sullivan, B. A. & Willard, H. F. Stable dicentric X chromosomes with two functional centromeres. Nature Genet. 20, 227–228 (1998).
Higgins, A. W., Schueler, M. G. & Willard, H. F. Chromosome engineering: generation of mono- and dicentric isochromosomes in a somatic cell hybrid system. Chromosoma 108, 256–265 (1999).
McClintock, B. The behaviour of successive nuclear divisions of a chromosome broken at meiosis. Proc. Natl Acad. Sci. USA 25, 405–416 (1939).
Agudo, M. et al. A dicentric chromosome of Drosophila melanogaster showing alternate centromere inactivation. Chromosoma 109, 190–196 (2000).
Faulkner, N. E., Vig, B., Echeverri, C. J., Wordeman, L. & Vallee, R. B. Localization of motor-related proteins and associated complexes to active, but not inactive, centromeres. Hum. Mol. Genet. 7, 671–677 (1998).
Sullivan, B. A. & Schwartz, S. Identification of centromeric antigens in dicentric Robertsonian translocations: CENP-C and CENP-E are necessary components of functional centromeres. Hum. Mol. Genet. 4, 2189–2197 (1995).
Depinet, T. W. et al. Characterization of neo-centromeres in marker chromosomes lacking detectable alpha-satellite DNA. Hum. Mol. Genet. 6, 1195–1204 (1997).
Du Sart, D. et al. A functional neo-centromere formed through activation of a latent human centromere and consisting of non-alpha-satellite DNA. Nature Genet. 16, 144–153 (1997).The first structural characterization of a human neocentromere.
Williams, B. C., Murphy, T. D., Goldberg, M. L. & Karpen, G. H. Neocentromere activity of structurally acentric mini-chromosomes in Drosophila. Nature Genet. 18, 30–37 (1998).
Warburton, P. E. et al. Molecular cytogenetic analysis of eight inversion duplications of human chromosome 13q that each contain a neocentromere. Am. J. Hum. Genet. 66, 1794–1806 (2000).
Saffery, R. et al. Human centromeres and neocentromeres show identical distribution patterns of >20 functionally important kinetochore-associated proteins. Hum. Mol. Genet. 9, 175–185 (2000).
Lo, A. W. I. et al. A novel chromatin immunoprecipitation and array (CIA) analysis identifies a 460-kb CENP-A-binding neocentromere DNA. Genome Res. 11, 448–457 (2001).
Lo, A. W. I. et al. A 330kb CENP-A binding domain and altered replication timing at a human neocentromere. EMBO J. 20, 1–10 (2001).Study that describes a neocentromeric sequence that associates with CENPA and a shift in replication timing of the CENPA-associated region compared with the endogenous locus from which it is derived.
Satinover, D. L., Vance, G. H., Van Dyke, D. L. & Schwartz, S. Cytogenetic analysis and construction of a BAC contig across a common neocentromeric region from 9p. Chromosoma (in the press).
Murphy, T. D. & Karpen, G. H. Centromeres take flight: α satellite and the quest for the human centromere. Cell 93, 317–320 (1998).
Maggert, K. A. & Karpen, G. H. Acquisition and metastability of centromere identity and function: sequence analysis of a human neocentromere. Genome Res. 10, 725–728 (2000).
Maggert, K. & Karpen, G. H. Neocentromere formation occurs by an activation mechanism that requires proximity to a functional centromere. Genetics 158 (in the press).First study of the mechanism of neocentromere formation, which shows that neocentromere formation in Drosophila requires proximity to a functional centromere and probably occurs by spreading of centromeric proteins onto non-centromeric DNA.
Bridger, J. M. & Bickmore, W. A. Putting the genome on the map. Trends Genet. 14, 403–409 (1998).
Brown, K. E. et al. Association of transcriptionally silent genes with Ikaros complexes at centromeric heterochromatin. Cell 91, 845–854 (1997).
Brown, K. E., Baxter, J., Graf, D., Merkenschlager, M. & Fisher, A. G. Dynamic repositioning of genes in the nucleus of lymphocytes preparing for cell division. Mol. Cell 3, 207–217 (1999).
Palmer, D. K., O'Day, K., Wener, M. H., Andrews, B. S. & Margolis, R. L. A 17-kD centromere protein (CENP-A) copurifies with nucleosome core particles and with histones. J. Cell Biol. 104, 805–815 (1987).
Palmer, D. K., O'Day, K., Trong, H. L., Charbonneau, H. & Margolis, R. L. Purification of the centromere-specific protein CENP-A and demonstration that it is a distinctive histone. Proc. Natl Acad. Sci. USA 88, 3734–3738 (1991).This paper and reference 65 describe the ground-breaking biochemical characterization of CENPA and the demonstration that it is a centromere-specific core histone.
Sullivan, K. F., Hechenberger, M. & Masri, K. Human CENP-A contains a histone H3 related histone fold domain that is required for targeting to the centromere. J. Cell Biol. 127, 581–592 (1994).
Meluh, P. B., Yang, P., Glowczewski, L., Koshland, D. & Smith, M. M. Cse4p is a component of the core centromere of Saccharomyces cerevisiae. Cell 94, 607–613 (1998).This paper describes chromatin immunoprecipitation studies that show that Cse4 is present in the Saccharomyces cerevisiae centromere.
Stoler, S., Keith, K. C., Curnick, K. E. & Fitzgerald-Hayes, M. A mutation in CSE4, an essential gene encoding a novel chromatin-associated protein in yeast, causes chromosome nondisjunction and cell cycle arrest at mitosis. Genes Dev. 9, 573–586 (1995).
Takahashi, K., Chen, E. S. & Yanagida, M. Requirement of Mis6 centromere connector for localizing a CENP-A-like protein in fission yeast. Science 288, 2215–2219 (2000).The initial characterization of the Schizosaccharomyces pombe homologue of CENPA and the first demonstration of a protein required for CENPA localization, Mis6.
Buchwitz, B. J., Ahmad, K., Moore, L. L., Roth, M. B. & Henikoff, S. A histone-H3-like protein in C. elegans. Nature 401, 547–548 (1999).
Henikoff, S., Ahmad, K., Platero, J. S. & Van Steensel, B. Heterochromatic deposition of centromeric histone H3-like proteins. Proc. Natl Acad. Sci. USA 97, 716–721 (2000).
Yoda, K. et al. Human centromere protein A (CENP-A) can replace histone H3 in nucleosome reconstitution in vitro. Proc. Natl Acad. Sci. USA 97, 7266–7271 (2000).
Shelby, R. D., Vafa, O. & Sullivan, K. F. Assembly of CENP-A into centromeric chromatin requires a cooperative array of nucleosomal DNA contact sites. J. Cell Biol. 136, 501–513 (1997).
Blower, M. D. & Karpen, G. H. The role of Drosophila CENP-A/CID in kinetochore formation, cell-cycle progression and interactions with heterochromatin. Nature Cell Biol. (in the press). Comprehensive study showing that Drosophila centromeres are composed of Cid-dependent multiple structural and functional domains and that Cid is required for many mitotic processes.
Howman, E. V. et al. Early disruption of centromeric chromatin organization in centromere protein A (Cenpa) null mice. Proc. Natl Acad. Sci. USA 97, 1148–1153 (2000).
Moore, L. L. & Roth, M. B. HCP-4, a CENP-C-like protein in Caenorhabditis elegans, is required for resolution of sister centromeres. J. Cell Biol. 153, 1199–1207 (2001).
Oegema, K., Desai, A., Rybina, S., Kirkham, M. & Hyman, A. Functional analysis of kinetochore assembly in Caenorhabditis elegans. J. Cell Biol. 153, 1209–1226 (2001).References 73 and 74 describe, for the first time, the organization and functional interactions between kinetochore proteins on holocentric chromosomes.
Nakaseko, Y., Goshima, G., Morishita, J. & Yanagida, M. M phase-specific kinetochore proteins in fission yeast. Microtubule-associating Dis1 and Mtc1 display rapid separation and segregation during anaphase. Curr. Biol. 11, 537–549 (2001).
Goshima, G., Saitoh, S. & Yanagida, M. Proper metaphase spindle length is determined by centromere proteins Mis12 and Mis6 required for faithful chromosome segregation. Genes Dev. 13, 1664–1677 (1999).
Ekwall, K. et al. The chromodomain protein Swi6: a key component at fission yeast centrome. Science 269, 1429–1431 (1995).
Rea, S. et al. Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature 406, 593–599 (2000).
Lachner, M., O'Carroll, D., Rea, S., Mechtler, K. & Jenuwein, T. Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410, 116–120 (2001).
Bannister, A. J. et al. Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain. Nature 410, 120–124 (2001).
Nakayama, J., Rice, J. C., Strahl, B. D., Allis, C. D. & Grewal, S. I. Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly. Science 292, 110–113 (2001).
Jenuwein, T. Re-SET-ting heterochromatin by histone methyltransferases. Trends Cell Biol. 11, 266–273 (2001).A recent review that describes newly defined histone modifications that are required to recruit proteins for establishment of heterochromatin structure. Also see references 78–81.
Adams, R. R., Maiato, H., Earnshaw, W. C. & Carmena, M. Essential roles of Drosophila inner centromere protein (incenp) and aurora b in histone h3 phosphorylation, metaphase chromosome alignment, kinetochore disjunction, and chromosome segregation. J. Cell Biol. 153, 865–880 (2001).
Lopez, J. M., Karpen, G. H. & Orr-Weaver, T. L. Sister-chromatid cohesion via MEI-S332 and kinetochore assembly are separable functions of the Drosophila centromere. Curr. Biol. 10, 997–1000 (2000).
Tanaka, T., Cosma, M. P., Wirth, K. & Nasmyth, K. Identification of cohesin association sites at centromeres and along chromosome arms. Cell 98, 847–858 (1999).
Adams, C. R. & Kamakaka, R. T. Chromatin assembly: biochemical identities and genetic redundancy. Curr. Opin. Genet. Dev. 9, 185–190 (1999).
Ridgway, P. & Almouzni, G. CAF-1 and the inheritance of chromatin states: at the crossroads of DNA replication and repair. J. Cell Sci. 113, 2647–2658 (2000).
Csink, A. K. & Henikoff, S. Something from nothing: the evolution and utility of satellite repeats. Trends Genet. 14, 200–204 (1998).
Ahmad, K. & Henikoff, S. Centromeres are specialized replication domains in heterochromatin. J. Cell Biol. 153, 101–109 (2001).
McCarroll, R. M. & Fangman, W. L. Time of replication of yeast centromeres and telomeRes. Cell 54, 505–513 (1988).
Shelby, R. D., Monier, K. & Sullivan, K. F. Chromatin assembly at kinetochores is uncoupled from DNA replication. J. Cell Biol. 151, 1113–1118 (2000).Excellent study showing that human centromeres are replicated asynchronously in mid- to late S phase and that CENPA assembly into centromeric nucleosomes is not dependent on DNA replication.
Sullivan, B. A. & Karpen, G. H. Centromere identity in Drosophila is not determined in vivo by replication timing. J. Cell Biol. (in the press).
Sullivan, K. F. & Shelby, R. D. Using time-lapse confocal microscopy for analysis of centromere dynamics in human cells. Methods Cell Biol. 58, 183–202 (1999).
Ortiz, J., Stemmann, O., Rank, S. & Lechner, J. A putative protein complex consisting of Ctf19, Mcm21, and Okp1 represents a missing link in the budding yeast kinetochore. Genes Dev. 13, 1140–1155 (1999).
Glowczewski, L., Yang, P., Kalashnikova, T., Santisteban, M. S. & Smith, M. M. Histone–histone interactions and centromere function. Mol. Cell. Biol. 20, 5700–5711 (2000).
Keith, K. C. & Fitzgerald-Hayes, M. CSE4 genetically interacts with the Saccharomyces cerevisiae centromere DNA elements CDE I and CDE II but not CDE III. Implications for the path of the centromere DNA around a Cse4p variant nucleosome. Genetics 156, 973–981 (2000).
Chen, Y. et al. The N terminus of the centromere H3-like protein Cse4p performs an essential function distinct from that of the histone fold domain. Mol. Cell. Biol. 20, 7037–7048 (2000).
Steiner, N. C. & Clarke, L. A novel epigenetic effect can alter centromere function in fission yeast. Cell 79, 865–874 (1994).The first clear demonstration of epigenetic effects on the function of the Schizosaccharomyces pombe centromere.
Zinkowski, R. P., Meyne, J. & Brinkley, B. R. The centromere–kinetochore complex: a repeat subunit model. J. Cell Biol. 113, 1091–1110 (1991).A classic paper on centromere structure that proposes that the centromere/kinetochore is composed of repeating subunits.
Seum, C., Delattre, M., Spierer, A. & Spierer, P. Ectopic HP1 promotes chromosome loops and variegated silencing in Drosophila. EMBO J. 20, 812–818 (2001).
Dobie, K., Hari, K., Maggert, K. & Karpen, G. H. Centromere proteins and chromosome inheritance: a complex affair. Curr. Opin. Genet. Dev. 9, 206–217 (1999).
Acknowledgements
We thank K. Sullivan for critical comments on the manuscript, and L. Moore and M. Roth (Fred Hutchison Cancer Research Center, Seattle) for the image in figure 2e. Our research on centromeres is supported by grants from the National Institutes of Health.
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Glossary
- ANEUPLOIDY
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The presence of extra copies, or no copies, of some chromosomes.
- CENTROMERE
-
The genetic locus required for chromosome segregation; contains DNA and proteins on which the kinetochore is formed.
- PLATEWARD METAPHASE MOVEMENTS
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(prometaphase congression). The movement of condensing chromosomes towards the metaphase plate, during which they capture spindle microtubules and orientate themselves in preparation for anaphase sister-chromatid separation.
- POLEWARD ANAPHASE MOVEMENTS
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The movement of chromatids along spindle microtubules towards the spindle poles.
- CENTROMERE REGION
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Chromatin and DNA in the vicinity of the functional centromere, including the pericentric heterochromatin.
- HETEROCHROMATIN
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A cytologically defined genomic component that contains repetitive DNA (highly repetitive satellite DNA, transposable elements and ribosomal DNA gene clusters) and some protein-coding genes. Most eukaryotic centromeres are embedded in heterochromatin.
- SPINDLE ASSEMBLY CHECKPOINT (SAC).
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A highly conserved surveillance mechanism in mitosis and meiosis that minimizes chromosome loss by preventing chromosomes from initiating anaphase until all kinetochores have successfully captured spindle microtubules.
- MONOCENTRIC
-
When a kinetochore forms on a specific, limited region of a chromosome.
- HOLOCENTRIC
-
When a kinetochore forms along the entire length of a chromosome.
- DYNEINS
-
Microtubule-based molecular motors that move towards the minus end of microtubules.
- KINESINS
-
Microtubule-based molecular motors that, in general, move towards the fast-growing, plus end of microtubules.
- EPIGENETIC
-
Any heritable influence (in the progeny of cells or of individuals) on chromosome or gene function that is not accompanied by a change in DNA sequence. Examples of epigenetic events include mammalian X-chromosome inactivation, imprinting, centromere inactivation and position effect variegation.
- POSITION EFFECT VARIEGATION (PEV).
-
The variable, heritable suppression of genes by their juxtaposition to heterochromatin or telomeres, or by movement of a gene into a different nuclear domain or chromosomal context.
- MINICHROMOSOME
-
An extranumerary chromosome that contains functional elements, such as telomeres and centromeres, and is transmitted in meiosis and mitosis.
- CENPA
-
A centromere-specific, histone H3-like protein.
- CENPC
-
A constitutive kinetochore protein. Its localization to the inner kinetochore is dependent on CENPA.
- CHP1
-
A Schizosaccharomyces pombe chromodomain protein.
- HETEROCHROMATIN PROTEIN 1 (Hp1)
-
A Drosophila heterochromatin protein that contains chromodomains.
- MEI-S332
-
A centromere-region protein involved in sister-chromatid cohesion.
- MIS6
-
A centromere protein that binds to the central core of the Schizosaccharomyces pombe centromere and is required to establish or maintain centromeric chromatin structure.
- SWI6
-
A chromodomain-containing Schizosaccharomyces pombe homologue of Drosophila heterochromatin protein 1. The chromodomain is a protein motif — common to proteins that in some cases interact with chromatin — that is involved in binding certain methylated histones; often associated with transcriptional repression.
- SU(VAR)3-9
-
A chromatin-binding translation initiation factor that suppresses position effect variegation in flies. Mammalian and Schizosaccharomyces pombe Su(Var)3-9 homologues are present in the centromere region of mitotic chromosomes, and encode a histone H3 methyltransferase.
- ANAPHASE BRIDGES
-
The physical stretching of dicentric chromosomes during anaphase due to the orientation and movement of linked kinetochores towards opposite spindle poles.
- NEOCENTROMERE
-
Chromosomal sites that do not contain typical repetitive centromeric DNA but do acquire centromeric chromatin, can assemble kinetochores, can recruit other centromeric proteins, and are transmitted faithfully in meiosis and mitosis.
- ACENTRIC
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A chromosome or chromosomal fragment that lacks a centromere.
- BOUNDARY ELEMENTS
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Chromatin that acts as an insulator to block changes in chromatin structure, protein binding, or the spreading of functional domains.
- HISTONE
-
A family of small, highly conserved basic proteins, found in the chromatin of all eukaryotic cells, that associate with DNA to form a nucleosome.
- CREST ANTISERA
-
Autoantibodies that recognize centromeric antigens (CENPs) found in the sera of patients with autoimmune diseases, such as CREST (calcinosis, Raynaud syndrome, oesophageal dysmotility, scleroderma and telangiectasia).
- NUCLEOSOME
-
The fundamental unit into which DNA and histones are packaged in eukaryotic cells.
- RNA INTERFERENCE (RNAi)
-
A process by which double-stranded RNA specifically silences the expression of homologous genes by degrading their cognate mRNA.
- CHROMATIN IMMUNOPRECIPITATION (ChIP)
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A technique that isolates sequences from soluble DNA chromatin extracts (complexes of DNA and protein) using antibodies that recognize specific chromosomal proteins.
- INNER CENTROMERE PROTEIN (Incenp)
-
A family of proteins that transiently localize to the region between sister-chromatid kinetochores during mitosis.
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Sullivan, B., Blower, M. & Karpen, G. Determining centromere identity: cyclical stories and forking paths. Nat Rev Genet 2, 584–596 (2001). https://doi.org/10.1038/35084512
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DOI: https://doi.org/10.1038/35084512
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