Skip to main content
PMC home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1992 Aug 2;118(4):759–773. doi: 10.1083/jcb.118.4.759

The Drosophila l(1)zw10 gene product, required for accurate mitotic chromosome segregation, is redistributed at anaphase onset

PMCID: PMC2289567  PMID: 1339459

Abstract

Mutations in the gene l(1)zw10 disrupt the accuracy of chromosome segregation in a variety of cell types during the course of Drosophila development. Cytological analysis of mutant larval brain neuroblasts shows very high levels of aneuploid cells. Many anaphase figures are aberrant, the most frequent abnormality being the presence of lagging chromosomes that remain in the vicinity of the metaphase plate when the other chromosomes have migrated toward the spindle poles. Finally, the centromeric connection between sister chromatids in mutant neuroblasts treated with colchicine often appears to be broken, in contrast with similarly treated control neuroblasts. The 85-kD protein encoded by the l(1)zw10 locus displays a dynamic pattern of localization in the course of the embryonic cell cycle. It is excluded from the nuclei during interphase, but migrates into the nuclear zone during prometaphase. At metaphase, the zw10 antigen is found in a novel filamentous structure that may be specifically associated with kinetochore microtubules. Upon anaphase onset, there is an extremely rapid redistribution of the zw10 protein to a location at or near the kinetochores of the separating chromosomes.

Full Text

The Full Text of this article is available as a PDF (4.9 MB).

Selected References

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

  1. Ault J. G., Nicklas R. B. Tension, microtubule rearrangements, and the proper distribution of chromosomes in mitosis. Chromosoma. 1989 Jun;98(1):33–39. doi: 10.1007/BF00293332. [DOI] [PubMed] [Google Scholar]
  2. Bernat R. L., Delannoy M. R., Rothfield N. F., Earnshaw W. C. Disruption of centromere assembly during interphase inhibits kinetochore morphogenesis and function in mitosis. Cell. 1991 Sep 20;66(6):1229–1238. doi: 10.1016/0092-8674(91)90045-z. [DOI] [PubMed] [Google Scholar]
  3. Bond B. J., Davidson N. The Drosophila melanogaster actin 5C gene uses two transcription initiation sites and three polyadenylation sites to express multiple mRNA species. Mol Cell Biol. 1986 Jun;6(6):2080–2088. doi: 10.1128/mcb.6.6.2080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brinkley B. R. Centromeres and kinetochores: integrated domains on eukaryotic chromosomes. Curr Opin Cell Biol. 1990 Jun;2(3):446–452. doi: 10.1016/0955-0674(90)90126-y. [DOI] [PubMed] [Google Scholar]
  5. Brinkley B. R., Tousson A., Valdivia M. M. The kinetochore of mammalian chromosomes: structure and function in normal mitosis and aneuploidy. Basic Life Sci. 1985;36:243–267. doi: 10.1007/978-1-4613-2127-9_16. [DOI] [PubMed] [Google Scholar]
  6. Brown N. H., Kafatos F. C. Functional cDNA libraries from Drosophila embryos. J Mol Biol. 1988 Sep 20;203(2):425–437. doi: 10.1016/0022-2836(88)90010-1. [DOI] [PubMed] [Google Scholar]
  7. Cavener D. R., Ray S. C. Eukaryotic start and stop translation sites. Nucleic Acids Res. 1991 Jun 25;19(12):3185–3192. doi: 10.1093/nar/19.12.3185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Compton D. A., Yen T. J., Cleveland D. W. Identification of novel centromere/kinetochore-associated proteins using monoclonal antibodies generated against human mitotic chromosome scaffolds. J Cell Biol. 1991 Mar;112(6):1083–1097. doi: 10.1083/jcb.112.6.1083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Davis B. K. Genetic analysis of a meiotic mutant resulting in precocious sister-centromere separation in Drosophila melanogaster. Mol Gen Genet. 1971;113(3):251–272. doi: 10.1007/BF00339546. [DOI] [PubMed] [Google Scholar]
  10. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dieckmann C. L., Tzagoloff A. Assembly of the mitochondrial membrane system. CBP6, a yeast nuclear gene necessary for synthesis of cytochrome b. J Biol Chem. 1985 Feb 10;260(3):1513–1520. [PubMed] [Google Scholar]
  12. Dombrádi V., Axton J. M., Glover D. M., Cohen P. T. Cloning and chromosomal localization of Drosophila cDNA encoding the catalytic subunit of protein phosphatase 1 alpha. High conservation between mammalian and insect sequences. Eur J Biochem. 1989 Aug 15;183(3):603–610. doi: 10.1111/j.1432-1033.1989.tb21089.x. [DOI] [PubMed] [Google Scholar]
  13. Driver A., Lacey S. F., Cullingford T. E., Mitchelson A., O'Hare K. Structural analysis of Doc transposable elements associated with mutations at the white and suppressor of forked loci of Drosophila melanogaster. Mol Gen Genet. 1989 Dec;220(1):49–52. doi: 10.1007/BF00260854. [DOI] [PubMed] [Google Scholar]
  14. Earnshaw W. C., Cooke C. A. Analysis of the distribution of the INCENPs throughout mitosis reveals the existence of a pathway of structural changes in the chromosomes during metaphase and early events in cleavage furrow formation. J Cell Sci. 1991 Apr;98(Pt 4):443–461. doi: 10.1242/jcs.98.4.443. [DOI] [PubMed] [Google Scholar]
  15. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  16. Foe V. E., Alberts B. M. Studies of nuclear and cytoplasmic behaviour during the five mitotic cycles that precede gastrulation in Drosophila embryogenesis. J Cell Sci. 1983 May;61:31–70. doi: 10.1242/jcs.61.1.31. [DOI] [PubMed] [Google Scholar]
  17. Foe V. E. Mitotic domains reveal early commitment of cells in Drosophila embryos. Development. 1989 Sep;107(1):1–22. [PubMed] [Google Scholar]
  18. Frasch M., Glover D. M., Saumweber H. Nuclear antigens follow different pathways into daughter nuclei during mitosis in early Drosophila embryos. J Cell Sci. 1986 Jun;82:155–172. doi: 10.1242/jcs.82.1.155. [DOI] [PubMed] [Google Scholar]
  19. Gatti M., Baker B. S. Genes controlling essential cell-cycle functions in Drosophila melanogaster. Genes Dev. 1989 Apr;3(4):438–453. doi: 10.1101/gad.3.4.438. [DOI] [PubMed] [Google Scholar]
  20. Gatti M., Goldberg M. L. Mutations affecting cell division in Drosophila. Methods Cell Biol. 1991;35:543–586. doi: 10.1016/s0091-679x(08)60587-7. [DOI] [PubMed] [Google Scholar]
  21. Gatti M., Tanzarella C., Olivieri G. Analysis of the chromosome aberrations induced by x-rays in somatic cells of Drosophila melanogaster. Genetics. 1974 Aug;77(4):701–719. doi: 10.1093/genetics/77.4.701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Goldberg M. L., Sheen J. Y., Gehring W. J., Green M. M. Unequal crossing-over associated with asymmetrical synapsis between nomadic elements in the Drosophila melanogaster genome. Proc Natl Acad Sci U S A. 1983 Aug;80(16):5017–5021. doi: 10.1073/pnas.80.16.5017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Goldstein L. S. Mechanisms of chromosome orientation revealed by two meiotic mutants in Drosophila melanogaster. Chromosoma. 1980;78(1):79–111. doi: 10.1007/BF00291909. [DOI] [PubMed] [Google Scholar]
  24. Gonzalez C., Casal Jimenez J., Ripoll P., Sunkel C. E. The spindle is required for the process of sister chromatid separation in Drosophila neuroblasts. Exp Cell Res. 1991 Jan;192(1):10–15. doi: 10.1016/0014-4827(91)90150-s. [DOI] [PubMed] [Google Scholar]
  25. González C., Casal J., Ripoll P. Functional monopolar spindles caused by mutation in mgr, a cell division gene of Drosophila melanogaster. J Cell Sci. 1988 Jan;89(Pt 1):39–47. doi: 10.1242/jcs.89.1.39. [DOI] [PubMed] [Google Scholar]
  26. Gunaratne P. H., Mansukhani A., Lipari S. E., Liou H. C., Martindale D. W., Goldberg M. L. Molecular cloning, germ-line transformation, and transcriptional analysis of the zeste locus of Drosophila melanogaster. Proc Natl Acad Sci U S A. 1986 Feb;83(3):701–705. doi: 10.1073/pnas.83.3.701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Guo L. H., Stepień P. P., Tso J. Y., Brousseau R., Narang S., Thomas D. Y., Wu R. Synthesis of human insulin gene. VIII. Construction of expression vectors for fused proinsulin production in Escherichia coli. Gene. 1984 Jul-Aug;29(1-2):251–254. doi: 10.1016/0378-1119(84)90186-0. [DOI] [PubMed] [Google Scholar]
  28. Henikoff S. Unidirectional digestion with exonuclease III creates targeted breakpoints for DNA sequencing. Gene. 1984 Jun;28(3):351–359. doi: 10.1016/0378-1119(84)90153-7. [DOI] [PubMed] [Google Scholar]
  29. Hiraoka Y., Agard D. A., Sedat J. W. Temporal and spatial coordination of chromosome movement, spindle formation, and nuclear envelope breakdown during prometaphase in Drosophila melanogaster embryos. J Cell Biol. 1990 Dec;111(6 Pt 2):2815–2828. doi: 10.1083/jcb.111.6.2815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Hoyt M. A., Totis L., Roberts B. T. S. cerevisiae genes required for cell cycle arrest in response to loss of microtubule function. Cell. 1991 Aug 9;66(3):507–517. doi: 10.1016/0092-8674(81)90014-3. [DOI] [PubMed] [Google Scholar]
  31. Jabs E. W., Tuck-Muller C. M., Cusano R., Rattner J. B. Studies of mitotic and centromeric abnormalities in Roberts syndrome: implications for a defect in the mitotic mechanism. Chromosoma. 1991 May;100(4):251–261. doi: 10.1007/BF00344159. [DOI] [PubMed] [Google Scholar]
  32. Judd B. H., Shen M. W., Kaufman T. C. The anatomy and function of a segment of the X chromosome of Drosophila melanogaster. Genetics. 1972 May;71(1):139–156. doi: 10.1093/genetics/71.1.139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Karess R. E., Glover D. M. rough deal: a gene required for proper mitotic segregation in Drosophila. J Cell Biol. 1989 Dec;109(6 Pt 1):2951–2961. doi: 10.1083/jcb.109.6.2951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Kellogg D. R., Field C. M., Alberts B. M. Identification of microtubule-associated proteins in the centrosome, spindle, and kinetochore of the early Drosophila embryo. J Cell Biol. 1989 Dec;109(6 Pt 1):2977–2991. doi: 10.1083/jcb.109.6.2977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Kerrebrock A. W., Miyazaki W. Y., Birnby D., Orr-Weaver T. L. The Drosophila mei-S332 gene promotes sister-chromatid cohesion in meiosis following kinetochore differentiation. Genetics. 1992 Apr;130(4):827–841. doi: 10.1093/genetics/130.4.827. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Kidd S., Lockett T. J., Young M. W. The Notch locus of Drosophila melanogaster. Cell. 1983 Sep;34(2):421–433. doi: 10.1016/0092-8674(83)90376-8. [DOI] [PubMed] [Google Scholar]
  37. Klemenz R., Weber U., Gehring W. J. The white gene as a marker in a new P-element vector for gene transfer in Drosophila. Nucleic Acids Res. 1987 May 26;15(10):3947–3959. doi: 10.1093/nar/15.10.3947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Li R., Murray A. W. Feedback control of mitosis in budding yeast. Cell. 1991 Aug 9;66(3):519–531. doi: 10.1016/0092-8674(81)90015-5. [DOI] [PubMed] [Google Scholar]
  39. Lin H. P., Church K. Meiosis in Drosophila melanogaster, III. The effect of orientation disruptor (ord) on gonial mitotic and the meiotic divisions in males. Genetics. 1982 Dec;102(4):751–770. doi: 10.1093/genetics/102.4.751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Lindsley D. L., Grell E. H. Spermiogenesis without chromosomes in Drosophila melanogaster. Genetics. 1969;61(1 Suppl):69–78. [PubMed] [Google Scholar]
  41. Mansukhani A., Crickmore A., Sherwood P. W., Goldberg M. L. DNA-binding properties of the Drosophila melanogaster zeste gene product. Mol Cell Biol. 1988 Feb;8(2):615–623. doi: 10.1128/mcb.8.2.615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Mansukhani A., Gunaratne P. H., Sherwood P. W., Sneath B. J., Goldberg M. L. Nucleotide sequence and structural analysis of the zeste locus of Drosophila melanogaster. Mol Gen Genet. 1988 Jan;211(1):121–128. doi: 10.1007/BF00338402. [DOI] [PubMed] [Google Scholar]
  43. McNeill P. A., Berns M. W. Chromosome behavior after laser microirradiation of a single kinetochore in mitotic PtK2 cells. J Cell Biol. 1981 Mar;88(3):543–553. doi: 10.1083/jcb.88.3.543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Moroi Y., Peebles C., Fritzler M. J., Steigerwald J., Tan E. M. Autoantibody to centromere (kinetochore) in scleroderma sera. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1627–1631. doi: 10.1073/pnas.77.3.1627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Murray A. W., Solomon M. J., Kirschner M. W. The role of cyclin synthesis and degradation in the control of maturation promoting factor activity. Nature. 1989 May 25;339(6222):280–286. doi: 10.1038/339280a0. [DOI] [PubMed] [Google Scholar]
  46. Murray A. W., Szostak J. W. Chromosome segregation in mitosis and meiosis. Annu Rev Cell Biol. 1985;1:289–315. doi: 10.1146/annurev.cb.01.110185.001445. [DOI] [PubMed] [Google Scholar]
  47. Olmsted J. B. Microtubule-associated proteins. Annu Rev Cell Biol. 1986;2:421–457. doi: 10.1146/annurev.cb.02.110186.002225. [DOI] [PubMed] [Google Scholar]
  48. Paddy M. R., Chelsky D. Spoke: a 120-kD protein associated with a novel filamentous structure on or near kinetochore microtubules in the mitotic spindle. J Cell Biol. 1991 Apr;113(1):161–171. doi: 10.1083/jcb.113.1.161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Pankov R., Lemieux M., Hancock R. An antigen located in the kinetochore region in metaphase and on polar microtubule ends in the midbody region in anaphase, characterised using a monoclonal antibody. Chromosoma. 1990 Apr;99(2):95–101. doi: 10.1007/BF01735324. [DOI] [PubMed] [Google Scholar]
  50. Perrimon N., Engstrom L., Mahowald A. P. Zygotic lethals with specific maternal effect phenotypes in Drosophila melanogaster. I. Loci on the X chromosome. Genetics. 1989 Feb;121(2):333–352. doi: 10.1093/genetics/121.2.333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Pfarr C. M., Coue M., Grissom P. M., Hays T. S., Porter M. E., McIntosh J. R. Cytoplasmic dynein is localized to kinetochores during mitosis. Nature. 1990 May 17;345(6272):263–265. doi: 10.1038/345263a0. [DOI] [PubMed] [Google Scholar]
  52. Pluta A. F., Cooke C. A., Earnshaw W. C. Structure of the human centromere at metaphase. Trends Biochem Sci. 1990 May;15(5):181–185. doi: 10.1016/0968-0004(90)90158-8. [DOI] [PubMed] [Google Scholar]
  53. Rieder C. L., Alexander S. P. The attachment of chromosomes to the mitotic spindle and the production of aneuploidy in newt lung cells. Prog Clin Biol Res. 1989;318:185–194. [PubMed] [Google Scholar]
  54. Robertson H. M., Preston C. R., Phillis R. W., Johnson-Schlitz D. M., Benz W. K., Engels W. R. A stable genomic source of P element transposase in Drosophila melanogaster. Genetics. 1988 Mar;118(3):461–470. doi: 10.1093/genetics/118.3.461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Shalloway D., Shenoy S. Oncoprotein kinases in mitosis. Adv Cancer Res. 1991;57:185–225. doi: 10.1016/s0065-230x(08)60999-9. [DOI] [PubMed] [Google Scholar]
  57. Shannon M. P., Kaufman T. C., Shen M. W., Judd B. H. Lethality patterns and morphology of selected lethal and semi-lethal mutations in the zeste-white region of Drosophila melanogaster. Genetics. 1972 Dec;72(4):615–638. doi: 10.1093/genetics/72.4.615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Smith D. A., Baker B. S., Gatti M. Mutations in genes encoding essential mitotic functions in Drosophila melanogaster. Genetics. 1985 Aug;110(4):647–670. doi: 10.1093/genetics/110.4.647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Stafstrom J. P., Staehelin L. A. Dynamics of the nuclear envelope and of nuclear pore complexes during mitosis in the Drosophila embryo. Eur J Cell Biol. 1984 May;34(1):179–189. [PubMed] [Google Scholar]
  60. Steuer E. R., Wordeman L., Schroer T. A., Sheetz M. P. Localization of cytoplasmic dynein to mitotic spindles and kinetochores. Nature. 1990 May 17;345(6272):266–268. doi: 10.1038/345266a0. [DOI] [PubMed] [Google Scholar]
  61. Warn R. M., Warn A. Microtubule arrays present during the syncytial and cellular blastoderm stages of the early Drosophila embryo. Exp Cell Res. 1986 Mar;163(1):201–210. doi: 10.1016/0014-4827(86)90573-2. [DOI] [PubMed] [Google Scholar]
  62. Wordeman L., Steuer E. R., Sheetz M. P., Mitchison T. Chemical subdomains within the kinetochore domain of isolated CHO mitotic chromosomes. J Cell Biol. 1991 Jul;114(2):285–294. doi: 10.1083/jcb.114.2.285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Xiao H., Lis J. T. Heat shock and developmental regulation of the Drosophila melanogaster hsp83 gene. Mol Cell Biol. 1989 Apr;9(4):1746–1753. doi: 10.1128/mcb.9.4.1746. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Zirkle R. E. Ultraviolet-microbeam irradiation of newt-cell cytoplasm: spindle destruction, false anaphase, and delay of true anaphase. Radiat Res. 1970 Mar;41(3):516–537. [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES