The activation of a neocentromere in Drosophila requires proximity to an endogenous centromere (original) (raw)

Abstract

The centromere is essential for proper segregation and inheritance of genetic information. Centromeres are generally regulated to occur exactly once per chromosome; failure to do so leads to chromosome loss or damage and loss of linked genetic material. The mechanism for faithful regulation of centromere activity and number is unknown. The presence of ectopic centromeres (neocentromeres) has allowed us to probe the requirements and characteristics of centromere activation, maintenance, and structure. We utilized chromosome derivatives that placed a 290-kilobase "test segment" in three different contexts within the Drosophila melanogaster genome--immediately adjacent to (1) centromeric chromatin, (2) centric heterochromatin, or (3) euchromatin. Using irradiation mutagenesis, we freed this test segment from the source chromosome and genetically assayed whether the liberated "test fragment" exhibited centromere activity. We observed that this test fragment behaved differently with respect to centromere activity when liberated from different chromosomal contexts, despite an apparent sequence identity. Test segments juxtaposed to an active centromere produced fragments with neocentromere activity, whereas test segments far from centromeres did not. Once established, neocentromere activity was stable. The imposition of neocentromere activity on juxtaposed DNA supports the hypothesis that centromere activity and identity is capable of spreading and is regulated epigenetically.

Full Text

The Full Text of this article is available as a PDF (296.7 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abad J. P., Agudo M., Molina I., Losada A., Ripoll P., Villasante A. Pericentromeric regions containing 1.688 satellite DNA sequences show anti-kinetochore antibody staining in prometaphase chromosomes of Drosophila melanogaster. Mol Gen Genet. 2000 Nov;264(4):371–377. doi: 10.1007/s004380000331. [DOI] [PubMed] [Google Scholar]
  2. Adams M. D., Celniker S. E., Holt R. A., Evans C. A., Gocayne J. D., Amanatides P. G., Scherer S. E., Li P. W., Hoskins R. A., Galle R. F. The genome sequence of Drosophila melanogaster. Science. 2000 Mar 24;287(5461):2185–2195. doi: 10.1126/science.287.5461.2185. [DOI] [PubMed] [Google Scholar]
  3. Agudo M., Abad J. P., Molina I., Losada A., Ripoll P., Villasante A. A dicentric chromosome of Drosophila melanogaster showing alternate centromere inactivation. Chromosoma. 2000 Jun;109(3):190–196. doi: 10.1007/s004120050427. [DOI] [PubMed] [Google Scholar]
  4. Ahmad K., Golic K. G. Telomere loss in somatic cells of Drosophila causes cell cycle arrest and apoptosis. Genetics. 1999 Mar;151(3):1041–1051. doi: 10.1093/genetics/151.3.1041. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Allshire R. C., Javerzat J. P., Redhead N. J., Cranston G. Position effect variegation at fission yeast centromeres. Cell. 1994 Jan 14;76(1):157–169. doi: 10.1016/0092-8674(94)90180-5. [DOI] [PubMed] [Google Scholar]
  6. 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. 1995 Jan 15;9(2):218–233. doi: 10.1101/gad.9.2.218. [DOI] [PubMed] [Google Scholar]
  7. Barry A. E., Bateman M., Howman E. V., Cancilla M. R., Tainton K. M., Irvine D. V., Saffery R., Choo K. H. The 10q25 neocentromere and its inactive progenitor have identical primary nucleotide sequence: further evidence for epigenetic modification. Genome Res. 2000 Jun;10(6):832–838. doi: 10.1101/gr.10.6.832. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Barry A. E., Howman E. V., Cancilla M. R., Saffery R., Choo K. H. Sequence analysis of an 80 kb human neocentromere. Hum Mol Genet. 1999 Feb;8(2):217–227. doi: 10.1093/hmg/8.2.217. [DOI] [PubMed] [Google Scholar]
  9. Biessmann H., Carter S. B., Mason J. M. Chromosome ends in Drosophila without telomeric DNA sequences. Proc Natl Acad Sci U S A. 1990 Mar;87(5):1758–1761. doi: 10.1073/pnas.87.5.1758. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cavalli G., Paro R. The Drosophila Fab-7 chromosomal element conveys epigenetic inheritance during mitosis and meiosis. Cell. 1998 May 15;93(4):505–518. doi: 10.1016/s0092-8674(00)81181-2. [DOI] [PubMed] [Google Scholar]
  11. Choo K. H. Centromere DNA dynamics: latent centromeres and neocentromere formation. Am J Hum Genet. 1997 Dec;61(6):1225–1233. doi: 10.1086/301657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Colot V., Maloisel L., Rossignol J. L. Interchromosomal transfer of epigenetic states in Ascobolus: transfer of DNA methylation is mechanistically related to homologous recombination. Cell. 1996 Sep 20;86(6):855–864. doi: 10.1016/s0092-8674(00)80161-0. [DOI] [PubMed] [Google Scholar]
  13. Csink A. K., Henikoff S. Something from nothing: the evolution and utility of satellite repeats. Trends Genet. 1998 May;14(5):200–204. doi: 10.1016/s0168-9525(98)01444-9. [DOI] [PubMed] [Google Scholar]
  14. Depinet T. W., Zackowski J. L., Earnshaw W. C., Kaffe S., Sekhon G. S., Stallard R., Sullivan B. A., Vance G. H., Van Dyke D. L., Willard H. F. Characterization of neo-centromeres in marker chromosomes lacking detectable alpha-satellite DNA. Hum Mol Genet. 1997 Aug;6(8):1195–1204. doi: 10.1093/hmg/6.8.1195. [DOI] [PubMed] [Google Scholar]
  15. Dernburg A. F., Broman K. W., Fung J. C., Marshall W. F., Philips J., Agard D. A., Sedat J. W. Perturbation of nuclear architecture by long-distance chromosome interactions. Cell. 1996 May 31;85(5):745–759. doi: 10.1016/s0092-8674(00)81240-4. [DOI] [PubMed] [Google Scholar]
  16. Dobie K. W., Hari K. L., Maggert K. A., Karpen G. H. Centromere proteins and chromosome inheritance: a complex affair. Curr Opin Genet Dev. 1999 Apr;9(2):206–217. doi: 10.1016/S0959-437X(99)80031-8. [DOI] [PubMed] [Google Scholar]
  17. Dobie K. W., Kennedy C. D., Velasco V. M., McGrath T. L., Weko J., Patterson R. W., Karpen G. H. Identification of chromosome inheritance modifiers in Drosophila melanogaster. Genetics. 2001 Apr;157(4):1623–1637. doi: 10.1093/genetics/157.4.1623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Dorer D. R., Henikoff S. Transgene repeat arrays interact with distant heterochromatin and cause silencing in cis and trans. Genetics. 1997 Nov;147(3):1181–1190. doi: 10.1093/genetics/147.3.1181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Dorn R., Krauss V., Reuter G., Saumweber H. The enhancer of position-effect variegation of Drosophila, E(var)3-93D, codes for a chromatin protein containing a conserved domain common to several transcriptional regulators. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):11376–11380. doi: 10.1073/pnas.90.23.11376. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ekwall K., Cranston G., Allshire R. C. Fission yeast mutants that alleviate transcriptional silencing in centromeric flanking repeats and disrupt chromosome segregation. Genetics. 1999 Nov;153(3):1153–1169. doi: 10.1093/genetics/153.3.1153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ekwall K., Olsson T., Turner B. M., Cranston G., Allshire R. C. Transient inhibition of histone deacetylation alters the structural and functional imprint at fission yeast centromeres. Cell. 1997 Dec 26;91(7):1021–1032. doi: 10.1016/s0092-8674(00)80492-4. [DOI] [PubMed] [Google Scholar]
  22. Espelin C. W., Kaplan K. B., Sorger P. K. Probing the architecture of a simple kinetochore using DNA-protein crosslinking. J Cell Biol. 1997 Dec 15;139(6):1383–1396. doi: 10.1083/jcb.139.6.1383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Farkas G., Leibovitch B. A., Elgin S. C. Chromatin organization and transcriptional control of gene expression in Drosophila. Gene. 2000 Aug 8;253(2):117–136. doi: 10.1016/s0378-1119(00)00240-7. [DOI] [PubMed] [Google Scholar]
  24. 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. 1998 Apr;7(4):671–677. doi: 10.1093/hmg/7.4.671. [DOI] [PubMed] [Google Scholar]
  25. Golic K. G., Golic M. M., Pimpinelli S. Imprinted control of gene activity in Drosophila. Curr Biol. 1998 Nov 19;8(23):1273–1276. doi: 10.1016/s0960-9822(07)00537-4. [DOI] [PubMed] [Google Scholar]
  26. Grewal S. I., Klar A. J. Chromosomal inheritance of epigenetic states in fission yeast during mitosis and meiosis. Cell. 1996 Jul 12;86(1):95–101. doi: 10.1016/s0092-8674(00)80080-x. [DOI] [PubMed] [Google Scholar]
  27. Henikoff S., Ahmad K., Platero J. S., van Steensel B. Heterochromatic deposition of centromeric histone H3-like proteins. Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):716–721. doi: 10.1073/pnas.97.2.716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Henikoff S. Nuclear organization and gene expression: homologous pairing and long-range interactions. Curr Opin Cell Biol. 1997 Jun;9(3):388–395. doi: 10.1016/s0955-0674(97)80012-9. [DOI] [PubMed] [Google Scholar]
  29. Hollick J. B., Dorweiler J. E., Chandler V. L. Paramutation and related allelic interactions. Trends Genet. 1997 Aug;13(8):302–308. doi: 10.1016/s0168-9525(97)01184-0. [DOI] [PubMed] [Google Scholar]
  30. Hyman A. A., Sorger P. K. Structure and function of kinetochores in budding yeast. Annu Rev Cell Dev Biol. 1995;11:471–495. doi: 10.1146/annurev.cb.11.110195.002351. [DOI] [PubMed] [Google Scholar]
  31. Ikeno M., Grimes B., Okazaki T., Nakano M., Saitoh K., Hoshino H., McGill N. I., Cooke H., Masumoto H. Construction of YAC-based mammalian artificial chromosomes. Nat Biotechnol. 1998 May;16(5):431–439. doi: 10.1038/nbt0598-431. [DOI] [PubMed] [Google Scholar]
  32. Karpen G. H., Allshire R. C. The case for epigenetic effects on centromere identity and function. Trends Genet. 1997 Dec;13(12):489–496. doi: 10.1016/s0168-9525(97)01298-5. [DOI] [PubMed] [Google Scholar]
  33. Karpen G. H., Le M. H., Le H. Centric heterochromatin and the efficiency of achiasmate disjunction in Drosophila female meiosis. Science. 1996 Jul 5;273(5271):118–122. doi: 10.1126/science.273.5271.118. [DOI] [PubMed] [Google Scholar]
  34. Karpen G. H., Spradling A. C. Analysis of subtelomeric heterochromatin in the Drosophila minichromosome Dp1187 by single P element insertional mutagenesis. Genetics. 1992 Nov;132(3):737–753. doi: 10.1093/genetics/132.3.737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Karpen G. H., Spradling A. C. Reduced DNA polytenization of a minichromosome region undergoing position-effect variegation in Drosophila. Cell. 1990 Oct 5;63(1):97–107. doi: 10.1016/0092-8674(90)90291-l. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Kelley R. L., Meller V. H., Gordadze P. R., Roman G., Davis R. L., Kuroda M. I. Epigenetic spreading of the Drosophila dosage compensation complex from roX RNA genes into flanking chromatin. Cell. 1999 Aug 20;98(4):513–522. doi: 10.1016/s0092-8674(00)81979-0. [DOI] [PubMed] [Google Scholar]
  37. Laurenti P., Graba Y., Rosset R., Pradel J. Genetic and molecular analysis of terminal deletions of chromosome 3R of Drosophila melanogaster. Gene. 1995 Mar 10;154(2):177–181. doi: 10.1016/0378-1119(94)00831-c. [DOI] [PubMed] [Google Scholar]
  38. Leach T. J., Chotkowski H. L., Wotring M. G., Dilwith R. L., Glaser R. L. Replication of heterochromatin and structure of polytene chromosomes. Mol Cell Biol. 2000 Sep;20(17):6308–6316. doi: 10.1128/mcb.20.17.6308-6316.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Lindsley D L, Novitski E. Localization of the Genetic Factors Responsible for the Kinetic Activity of X Chromosomes of Drosophila Melanogaster. Genetics. 1958 Sep;43(5):790–798. doi: 10.1093/genetics/43.5.790. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Lindsley D. L., Sandler L., Baker B. S., Carpenter A. T., Denell R. E., Hall J. C., Jacobs P. A., Miklos G. L., Davis B. K., Gethmann R. C. Segmental aneuploidy and the genetic gross structure of the Drosophila genome. Genetics. 1972 May;71(1):157–184. doi: 10.1093/genetics/71.1.157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. 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. 2000 Aug 24;10(16):997–1000. doi: 10.1016/s0960-9822(00)00650-3. [DOI] [PubMed] [Google Scholar]
  42. Losada A., Abad J. P., Villasante A. Organization of DNA sequences near the centromere of the Drosophila melanogaster Y chromosome. Chromosoma. 1997 Dec;106(8):503–512. doi: 10.1007/s004120050272. [DOI] [PubMed] [Google Scholar]
  43. Lyko F., Ramsahoye B. H., Jaenisch R. DNA methylation in Drosophila melanogaster. Nature. 2000 Nov 30;408(6812):538–540. doi: 10.1038/35046205. [DOI] [PubMed] [Google Scholar]
  44. Maggert K. A., Karpen G. H. Acquisition and metastability of centromere identity and function: sequence analysis of a human neocentromere. Genome Res. 2000 Jun;10(6):725–728. doi: 10.1101/gr.10.6.725. [DOI] [PubMed] [Google Scholar]
  45. Mason J. M., Strobel E., Green M. M. mu-2: mutator gene in Drosophila that potentiates the induction of terminal deficiencies. Proc Natl Acad Sci U S A. 1984 Oct;81(19):6090–6094. doi: 10.1073/pnas.81.19.6090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Murphy T. D., Karpen G. H. Centromeres take flight: alpha satellite and the quest for the human centromere. Cell. 1998 May 1;93(3):317–320. doi: 10.1016/s0092-8674(00)81158-7. [DOI] [PubMed] [Google Scholar]
  47. Murphy T. D., Karpen G. H. Interactions between the nod+ kinesin-like gene and extracentromeric sequences are required for transmission of a Drosophila minichromosome. Cell. 1995 Apr 7;81(1):139–148. doi: 10.1016/0092-8674(95)90378-x. [DOI] [PubMed] [Google Scholar]
  48. Novitski E. The Genetic Consequences of Anaphase Bridge Formation in Drosophila. Genetics. 1952 May;37(3):270–287. doi: 10.1093/genetics/37.3.270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Oleinick N. L., Balasubramaniam U., Xue L., Chiu S. Nuclear structure and the microdistribution of radiation damage in DNA. Int J Radiat Biol. 1994 Nov;66(5):523–529. doi: 10.1080/09553009414551561. [DOI] [PubMed] [Google Scholar]
  50. Page S. L., Shaffer L. G. Chromosome stability is maintained by short intercentromeric distance in functionally dicentric human Robertsonian translocations. Chromosome Res. 1998 Feb;6(2):115–122. doi: 10.1023/a:1009286929145. [DOI] [PubMed] [Google Scholar]
  51. 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 U S A. 1991 May 1;88(9):3734–3738. doi: 10.1073/pnas.88.9.3734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Partridge J. F., Borgstrøm B., Allshire R. C. Distinct protein interaction domains and protein spreading in a complex centromere. Genes Dev. 2000 Apr 1;14(7):783–791. [PMC free article] [PubMed] [Google Scholar]
  53. Pluta A. F., Mackay A. M., Ainsztein A. M., Goldberg I. G., Earnshaw W. C. The centromere: hub of chromosomal activities. Science. 1995 Dec 8;270(5242):1591–1594. doi: 10.1126/science.270.5242.1591. [DOI] [PubMed] [Google Scholar]
  54. Saffery R., Irvine D. V., Griffiths B., Kalitsis P., Wordeman L., Choo K. H. Human centromeres and neocentromeres show identical distribution patterns of >20 functionally important kinetochore-associated proteins. Hum Mol Genet. 2000 Jan 22;9(2):175–185. doi: 10.1093/hmg/9.2.175. [DOI] [PubMed] [Google Scholar]
  55. Shelby R. D., Monier K., Sullivan K. F. Chromatin assembly at kinetochores is uncoupled from DNA replication. J Cell Biol. 2000 Nov 27;151(5):1113–1118. doi: 10.1083/jcb.151.5.1113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Starr D. A., Williams B. C., Hays T. S., Goldberg M. L. ZW10 helps recruit dynactin and dynein to the kinetochore. J Cell Biol. 1998 Aug 10;142(3):763–774. doi: 10.1083/jcb.142.3.763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Steiner N. C., Clarke L. A novel epigenetic effect can alter centromere function in fission yeast. Cell. 1994 Dec 2;79(5):865–874. doi: 10.1016/0092-8674(94)90075-2. [DOI] [PubMed] [Google Scholar]
  58. Sullivan B. A., Willard H. F. Stable dicentric X chromosomes with two functional centromeres. Nat Genet. 1998 Nov;20(3):227–228. doi: 10.1038/3024. [DOI] [PubMed] [Google Scholar]
  59. 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. 1994 Nov;127(3):581–592. doi: 10.1083/jcb.127.3.581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Sun X., Wahlstrom J., Karpen G. Molecular structure of a functional Drosophila centromere. Cell. 1997 Dec 26;91(7):1007–1019. doi: 10.1016/s0092-8674(00)80491-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Sunkel C. E., Coelho P. A. The elusive centromere: sequence divergence and functional conservation. Curr Opin Genet Dev. 1995 Dec;5(6):756–767. doi: 10.1016/0959-437x(95)80008-s. [DOI] [PubMed] [Google Scholar]
  62. Talbert P. B., Henikoff S. A reexamination of spreading of position-effect variegation in the white-roughest region of Drosophila melanogaster. Genetics. 2000 Jan;154(1):259–272. doi: 10.1093/genetics/154.1.259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Thon G., Friis T. Epigenetic inheritance of transcriptional silencing and switching competence in fission yeast. Genetics. 1997 Mar;145(3):685–696. doi: 10.1093/genetics/145.3.685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Tolchkov E. V., Rasheva V. I., Bonaccorsi S., Westphal T., Gvozdev V. A. The size and internal structure of a heterochromatic block determine its ability to induce position effect variegation in Drosophila melanogaster. Genetics. 2000 Apr;154(4):1611–1626. doi: 10.1093/genetics/154.4.1611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Tower J., Karpen G. H., Craig N., Spradling A. C. Preferential transposition of Drosophila P elements to nearby chromosomal sites. Genetics. 1993 Feb;133(2):347–359. doi: 10.1093/genetics/133.2.347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Vafa O., Sullivan K. F. Chromatin containing CENP-A and alpha-satellite DNA is a major component of the inner kinetochore plate. Curr Biol. 1997 Nov 1;7(11):897–900. doi: 10.1016/s0960-9822(06)00381-2. [DOI] [PubMed] [Google Scholar]
  67. Vig B. K., Latour D., Brown M. Localization of anti-CENP antibodies and alphoid sequences in acentric heterochromatin in a breast cancer cell line. Cancer Genet Cytogenet. 1996 Jun;88(2):118–125. doi: 10.1016/0165-4608(95)00210-3. [DOI] [PubMed] [Google Scholar]
  68. Vig B. K. Sequence of centromere separation: role of centromeric heterochromatin. Genetics. 1982 Dec;102(4):795–806. doi: 10.1093/genetics/102.4.795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Wakimoto B. T. Beyond the nucleosome: epigenetic aspects of position-effect variegation in Drosophila. Cell. 1998 May 1;93(3):321–324. doi: 10.1016/s0092-8674(00)81159-9. [DOI] [PubMed] [Google Scholar]
  70. Wallrath L. L. Unfolding the mysteries of heterochromatin. Curr Opin Genet Dev. 1998 Apr;8(2):147–153. doi: 10.1016/s0959-437x(98)80135-4. [DOI] [PubMed] [Google Scholar]
  71. Warburton P. E., Cooke H. J. Hamster chromosomes containing amplified human alpha-satellite DNA show delayed sister chromatid separation in the absence of de novo kinetochore formation. Chromosoma. 1997 Aug;106(3):149–159. doi: 10.1007/s004120050234. [DOI] [PubMed] [Google Scholar]
  72. Warburton P. E., Dolled M., Mahmood R., Alonso A., Li S., Naritomi K., Tohma T., Nagai T., Hasegawa T., Ohashi H. Molecular cytogenetic analysis of eight inversion duplications of human chromosome 13q that each contain a neocentromere. Am J Hum Genet. 2000 Apr 24;66(6):1794–1806. doi: 10.1086/302924. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Wiens G. R., Sorger P. K. Centromeric chromatin and epigenetic effects in kinetochore assembly. Cell. 1998 May 1;93(3):313–316. doi: 10.1016/s0092-8674(00)81157-5. [DOI] [PubMed] [Google Scholar]
  74. Willard H. F. Centromeres of mammalian chromosomes. Trends Genet. 1990 Dec;6(12):410–416. doi: 10.1016/0168-9525(90)90302-m. [DOI] [PubMed] [Google Scholar]
  75. Willard H. F. Human artificial chromosomes coming into focus. Nat Biotechnol. 1998 May;16(5):415–416. doi: 10.1038/nbt0598-415. [DOI] [PubMed] [Google Scholar]
  76. Williams B. C., Murphy T. D., Goldberg M. L., Karpen G. H. Neocentromere activity of structurally acentric mini-chromosomes in Drosophila. Nat Genet. 1998 Jan;18(1):30–37. doi: 10.1038/ng0198-30. [DOI] [PubMed] [Google Scholar]
  77. Wines D. R., Henikoff S. Somatic instability of a Drosophila chromosome. Genetics. 1992 Jul;131(3):683–691. doi: 10.1093/genetics/131.3.683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Zinkowski R. P., Meyne J., Brinkley B. R. The centromere-kinetochore complex: a repeat subunit model. J Cell Biol. 1991 Jun;113(5):1091–1110. doi: 10.1083/jcb.113.5.1091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. du Sart D., Cancilla M. R., Earle E., Mao J. I., Saffery R., Tainton K. M., Kalitsis P., Martyn J., Barry A. E., Choo K. H. A functional neo-centromere formed through activation of a latent human centromere and consisting of non-alpha-satellite DNA. Nat Genet. 1997 Jun;16(2):144–153. doi: 10.1038/ng0697-144. [DOI] [PubMed] [Google Scholar]