Abstract
Chromosome fragments that lack centromeric DNA (structurally acentric chromosomes) are usually not inherited in mitosis and meiosis. We previously described the isolation, after irradiation of a Drosophila melanogaster mini-chromosome, of structurally acentric mini-chromosomes that display efficient mitotic and meiotic transmission despite their small size (under 300 kb) and lack of centromeric DNA. Here we report that these acentric mini-chromosomes bind the centromere-specific protein ZW10 and associate with the spindle poles in anaphase. The sequences in these acentric mini-chromosomes were derived from the tip of the X chromosome, which does not display centromere activity or localize ZW10, even when separated from the rest of the X. We conclude that the normally non-centromeric DNAs present in these acentric mini-chromosomes have acquired centromere function, and suggest that this example of ‘neocentromere’ formation involves appropriation of a self-propagating centromeric chromatin structure. The potential relevance of these observations to the identity, propagation and function of normal centromeres is discussed.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Pluta, A.F., Mackay, A.M, Ainsztein, A.M., Goldberg, I.G. & Earnshaw, W.C. The centromere: hub of chromosomal activities. Science 270, 1591–1594 (1995).
Goldstein, L.S. Kinetochore structure and its role tn chromosome orientation during the first meiotic division in male D. melanogaster. Cell 25, 591–602 (1981).
Brinkley, B.R. Chromosomes, kinetochores and the microtubule connection. B/oessays 13, 675–681 (1991).
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.
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).
Brown, M.T. Sequence similarities between the yeast chromosome segregation protein Mif2 and the mammalian centromere protein CENP-C. Gene 160, 111–116 (1995).
Meluh, P.B. & Koshland, D., Evidence that the MIF2 gene of Saccharomyces cerevisiae encodes a centromere protein with homology to the mammalian centromere protein CENP-C. Mol. Biol. Cell 6, 793–807 (1995).
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).
Starr, D.A. et al. Conservation of the centromere/kinetochore protein ZW10. J. Cell Biol. 138, 1289–1301 (1997).
Wevrick, R., Willard, V.P., & Willard, H.F., Structure of DNA near long tandem arrays of alpha satellite DNA at the centromere of human chromosome 7. Genomics 14, 912–923 (1992).
Le, M.-H., Duricka, D. & Karpen, G.H. Islands of complex DNA are widespread in Drosophila centric heterochromatin. Genetics 141, 283–303 (1995).
Lohe, A.R. & Hilliker, A.J. Return of the H-word (heterochromatin). Curr. Opin. Genet. Dev. 5, 746–755 (1995).
Karpen, G.H . & Allshire, R. The case for epigenetic effects on centromere identity and function. Trends Genet. 13, 489–496 (1997).
Page, S.L, Earnshaw, W.C., Choo, K.H.A. & Shatter, L.G. Further evidence that CENP-C is a necessary component of active centromeres: studies of a dic(X; 15) with simultaneous immunofluorescence and FISH. Hum. Mol. Genet. 4, 289–294 (1995).
Steiner, N.C. & Clarke, L. A novel epigenetic effect can alter centromere function in fission yeast. Cell 79, 865–874 (1994).
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).
Voullaire, L.E., Slater, H.R., & Choo, K.H.A. A functional marker centromere with no detectable alpha-satellite, satellite III, or CENP-B protein: activation of a latent centromere? Am. J. Hum. Genet. 52, 1153–1163 (1993).
Brown, W. & Tyler-Smith, C. Centromere activation. Trends Genet. 11, 337–339 (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).
Karpen, G.H. & Spradling, A.C. Analysis of sub-telomeric heterochromatin in the Drosophila mini-chromosome Dp1187 by single P element insertional mutagenesis. Genetics 132, 737–753 (1992).
Murphy, T.D. & Karpen, G.H. Localization of centromere function in a Drosophila mini-chromosome. Cell 82, 599–609 (1995).
Sun, X., Wahlstrom, J. & Karpen, G.H. Molecular structure of a functional Drosophila centromere. Cell 91, (1997).
Mather, K. & Stone, L.H.A. The effects of X-radiation upon somatic chromosomes. J. Genet. 28, 1–24 (1933).
Rieder, C.L, Davison, E.A., Jensen, L.C., Cassimeris, L. & Salmon, E.D. Oscillatory movements of monooriented chromosomes and their position relative to the spindle pole result from the ejection properties of the aster and half-spindle. J. Cell Biol. 103, 581–591 (1986).
Khodjakov, A., Cole, R.W., Bajer, A.S. & Rieder, C.L. The force for poleward chromosome motion in Haemanthus cells acts along the length of the chromosome during metaphase but only at the kinetochore during anaphase. J. Cell Biol. 132, 1093–1104 (1996).
Williams, B.C., Karr, T.L, Montgomery, J.M. & Goldberg, M.L The Drosophila I(1)zw10 gene product, required for accurate mitotic chromosome segregation, is redistributed at anaphase onset. J. Cell Biol. 118, 759–773 (1992).
Williams, B.C. & Goldberg, M.L. Determinants of Drosophila zw10 protein localization and function. J Cell Sci. 107, 785–798 (1994).
Williams, B.C., Gatti, M. & Goldberg, M.L Bipolar spindle attachments affect redistributions of ZW10, a Drosophila centromere/kinetochore component required for accurate chromosome segregation. J. Cell Biol. 134, 1127–1140 (1996).
Rudner, A.D. & Murray, A.W. The spindle assembly checkpoint. Curr. Opin. Cell Biol. 8, 773–780 (1996).
Murphy, T.D. & Karpen, G.H. Interactions between the nod+ kinesin-like gene and extracentromeric sequences are required for transmission of a Drosophila mini-chromosome. Cell 81, 139–148 (1995).
Cook, K.R., Murphy, T.D., Nguyen, T.C. & Karpen, G.H. Identification of trans-acting genes necessary for centromere function in Drosophila melanogaster using centromere-defective mini-chromosomes. Genetics 145, 737–747 (1997).
Theurkauf, W.E. & Hawley, R.S. Meiotic spindle assembly in Drosophila females: behavior of nonexchange chromosomes and the effects of mutations in the nod kinesin-like protein. J. Cell Biol. 116, 1167–1180 (1992).
Afshar, K., Barton, N.R., Hawley, R.S. & Goldstein, L.S.B. DNA binding and meiotic chromosomal localization of the Drosophila nod kinesin-like protein. Cell 81, 129–138 (1995).
Karpen, G.H. & Spradling, A.C. Reduced DNA polytenization of a mini-chromosome region undergoing position-effect variegation in Drosophila. Cell 63, 97–107 (1990).
Tower, J., Karpen, G.H., Craig, N. & Spradling, A.C. Preferential transposition of Drosophila P elements to nearby chromosomal sites. Genetics 133, 347–359 (1993).
Mason, J.M. & Biessmann, H. The unusual telomeres of Drosophila. Trends Genet. 11, 58–62 (1995).
Lindsley, D.L. & Zimm, G.G. The Genome of Drosophila Melanogaster (Academic, San Diego, California, 1992).
Golic, K.G. Local transposition of P elements in Drosophila melanogaster and recombination between duplicated elements using a site-specific recombinase. Genetics 137, 551–563 (1994).
Bonner, J.J., Parks, C., Parker-Thornburg, J., Mortin, M.A. & Pelham, H.R. The use of promoter fusions in Drosophila genetics: isolation of mutations affecting the heat shock response. Cell 37, 979–991 (1984).
Cenci, G. et al. UbcD1, a Drosophila ubiquitin-conjugating enzyme required for proper telomere behavior. 11, 863–875 (1997).
Rhoades, M.M. Heterosis (ed. Gowen, J.W.) 66-80 (Iowa State College, Ames, Iowa, 1952).
Dawe, R.K. & Cande, W.Z. Induction of centromeric activity in maize by suppressor of meiotic drive 1. Proc, Natl. Acad. Sci. USA 93, 8512–8517 (1996).
Alfenito, M.R. & Birchler, J.A. Molecular characterization of a maize B chromosome centric sequence. Genetics 135, 589–597 (1993).
Pimpinelli, S. & Goday, C. Unusual kinetochores and chromatin diminution in Parascaris. Trends Genet. 5, 310–315 (1989).
Albertson, D.G., Rose, A.M. & Villeneuve, A.M. The Nematode C. Elegans (eds Riddle, D.L, Blumenthal, T, Meyer, B.J. & Priess, J.R.) 47–78 (Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 1997).
Herzing, L.B.K., Romer, J.T., Horn, J.M. & Ashworth, A. Xist has properties of the X-chromosome inactivation centre. Nature 386, 272–275 (1997).
Ajiro, K. & Nishimoto, T. Specific site of histone H3 phosphorylation related to the maintenance of premature chromosome condensation: evidence for catalytically induced interchange of the subunits. J. Biol. Chem. 260, 15379–15381 (1985).
Turner, B. & O'Neill, L. Histone acetylation in chromatin and chromosomes. Semin. Cell Biol. 6, 229–236 (1995).
Wolffe, A. & Pruss, D. Targeting chromatin disruption: transcription regulators that acetylate histones. Cell 84, 817–819 (1996).
Karpen, G.H. Position-effect variegation and the new biology of heterochromatin. Curr. Opin. Genet. Dev. 4, 281–291 (1994).
Clarke, L, Baum, M., Marschall, L.G., Ngan, V.K. & Steiner, N.C. Structure and function of Schizosaccharomyces pombe centromeres. Cold Spring Harb. Symp. Quant Biol. 58, 687–695 (1993).
Allshire, R.C., Javerzat, J.P., Redhead, N.J. & Cranston, G. Position effect variegation at fission yeast centromeres. Cell 76, 157–169 (1994).
Marschall, L.G. & Clarke, L. A novel cis-acting centromeric DNA element affects S. pombe centromeric chromatin structure at a distance. J. Cell Biol. 128, 445-454 (1995).
Ngan, V.K. & Clarke, L. The centromere enhancer mediates centromere activation in Schizosaccharomyces pombe. Mol. Cell Biol. 17, 3305–3314 (1997).
Haaf, T., Warburton, P.E. & Willard, H.F. Integration of human alpha-satellite DNA into simian chromosomes: centromere protein binding and disruption of normal chromosome segregation. Cell 70, 681–696 (1992).
Larin, Z., Fricker, M.D. & Tyler-Smith, C. De novo formation of several features of a centromere following introduction of a Y alphoid YAC into mammalian cells. Hum. Mol. Genet. 3, 689–695 (1994).
Taylor, S.S., Larin, Z. & Tyler-Smith, C. Analysis of extrachromosomal structures containing human centromeric alphoid satellite DNA sequences in mouse cells. Chromosoma 105, 70–81 (1996).
Warburton, P.E. & Cooke, HJ. Hamster chromosomes containing amplified human oc-satellite DNA show delayed sister chromatid separation in the absence of de novo kinetochore formation. Chromosoma 106, 149–159 (1997).
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).
Therman, E., Sarto, G.E. & Patau, K. Apparently isodicentric but functionally monocentric X chromosome in man. Am. J. Hum. Genet. 26, 83–92 (1974).
Merry, D.E., Pathak, S., Hsu, T.C. & Brinkley, B.R. Anti-kinetochore antibodies: use as probes for inactive centromeres. Am. J. Hum. Genet. 37, 425–430 (1985).
Earnshaw, W.C., Ratrie, H. & Stetten, G. Visualization of centromere proteins CENP-B and CENP-C on a stable dicentric chromosome in cytological spreads. Chromosoma 98, 1–12 (1989).
Ault, J.G. & Lyttle, T.W. A transmissible dicentric chromosome in Drosophila melanogaster. Chromosoma 97, 71–79 (1988).
Lindsley, D.L. & Tokuyasu, K.T. in The Genetics and Biology of Drosophila (eds Ashburner, M. & Wright, T.R.F.) 225–294 (Academic, London, 1980).
McKee, B.D. & Karpen, G.H. Drosophila ribosomal RNA genes function as an X-Y pairing site during male meiosis. Cell 61, 61–72 (1990).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Williams, B., Murphy, T., Goldberg, M. et al. Neocentromere activity of structurally acentric mini-chromosomes in Drosophila. Nat Genet 18, 30–38 (1998). https://doi.org/10.1038/ng0198-30
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/ng0198-30
This article is cited by
-
Epigenetic control of centromere: what can we learn from neocentromere?
Genes & Genomics (2022)
-
Genetic and epigenetic effects on centromere establishment
Chromosoma (2020)
-
The dark side of centromeres: types, causes and consequences of structural abnormalities implicating centromeric DNA
Nature Communications (2018)
-
Inheritance of the CENP-A chromatin domain is spatially and temporally constrained at human centromeres
Epigenetics & Chromatin (2016)
-
The molecular basis for centromere identity and function
Nature Reviews Molecular Cell Biology (2016)