NuMA is required for the proper completion of mitosis

doi:10.1083/jcb.120.4.947

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NuMA is required for the proper completion of mitosis

DA Compton and DW Cleveland
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.

NuMA is a 236-kD intranuclear protein that during mitosis is distributed into each daughter cell by association with the pericentrosomal domain of the spindle apparatus. The NuMA polypeptide consists of globular head and tail domains separated by a discontinuous 1500 amino acid coiled-coil spacer. Expression of human NuMA lacking its globular head domain results in cells that fail to undergo cytokinesis and assemble multiple small nuclei (micronuclei) in the subsequent interphase despite the appropriate localization of the truncated NuMA to both the nucleus and spindle poles. This dominant phenotype is morphologically identical to that of the tsBN2 cell line that carries a temperature-sensitive mutation in the chromatin-binding protein RCC1. At the restrictive temperature, these cells end mitosis without completing cytokinesis followed by micronucleation in the subsequent interphase. We demonstrate that the wild-type NuMA is degraded in the latest mitotic stages in these mutant cells and that NuMA is excluded from the micronuclei that assemble post-mitotically. Elevation of NuMA levels in these mutant cells by forcing the expression of wild-type NuMA is sufficient to restore post-mitotic assembly of a single normal-sized nucleus. Expression of human NuMA lacking its globular tail domain results in NuMA that fails both to target to interphase nuclei and to bind to the mitotic spindle. In the presence of this mutant, cells transit through mitosis normally, but assemble micronuclei in each daughter cell. The sum of these findings demonstrate that NuMA function is required during mitosis for the terminal phases of chromosome separation and/or nuclear reassembly.
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Krauss, S. W., Heald, R., Lee, G., Nunomura, W., Gimm, J. A., Mohandas, N., Chasis, J. A. (2002). Two Distinct Domains of Protein 4.1 Critical for Assembly of Functional Nuclei in Vitro. J. Biol. Chem. 277: 44339-44346 [Abstract] [Full Text]
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Melnick, A., Licht, J. D. (1999). Deconstructing a Disease: RAR{alpha}, Its Fusion Partners, and Their Roles in the Pathogenesis of Acute Promyelocytic Leukemia. Blood 93: 3167-3215 [Full Text]
Mattagajasingh, S. N., Huang, S.-C., Hartenstein, J. S., Snyder, M., Marchesi, V. T., Benz, E. J. Jr. (1999). A Nonerythroid Isoform of Protein 4.1R Interacts with the Nuclear Mitotic Apparatus (NuMA) Protein. JCB 145: 29-43 [Abstract] [Full Text]
Zatsepina, O., Rousselet, A, Chan, P., Olson, M., Jordan, E., Bornens, M (1999). The nucleolar phosphoprotein B23 redistributes in part to the spindle poles during mitosis. J. Cell Sci. 112: 455-466 [Abstract]
Hsu, L.-C., White, R. L. (1998). BRCA1 is associated with the centrosome during mitosis. Proc. Natl. Acad. Sci. USA 95: 12983-12988 [Abstract] [Full Text]
Dujardin, D., Wacker, U. I., Moreau, A., Schroer, T. A., Rickard, J. E., De Mey, J. R. (1998). Evidence for a Role of CLIP-170 in the Establishment of Metaphase Chromosome Alignment. JCB 141: 849-862 [Abstract] [Full Text]
Sodja, C, Brown, D., Walker, P., Chaly, N (1998). Splenic T lymphocytes die preferentially during heat-induced apoptosis: NuMA reorganization as a marker. J. Cell Sci. 111: 2305-2313 [Abstract]
Loyer, P, Trembley, J., Lahti, J., Kidd, V. (1998). The RNP protein, RNPS1, associates with specific isoforms of the p34cdc2-related PITSLRE protein kinase in vivo. J. Cell Sci. 111: 1495-1506 [Abstract]
Merdes, A, Cleveland, D. (1998). The role of NuMA in the interphase nucleus. J. Cell Sci. 111: 71-79 [Abstract]
Gaglio, T., Dionne, M. A., Compton, D. A. (1997). Mitotic Spindle Poles are Organized by Structural and Motor Proteins in Addition to Centrosomes. JCB 138: 1055-1066 [Abstract] [Full Text]
Heald, R., Tournebize, R., Habermann, A., Karsenti, E., Hyman, A. (1997). Spindle Assembly in Xenopus Egg Extracts: Respective Roles of Centrosomes and Microtubule Self-Organization. JCB 138: 615-628 [Abstract] [Full Text]
Amann, J., Kidd, V. J., Lahti, J. M. (1997). Characterization of Putative Human Homologues of the Yeast Chromosome Transmission Fidelity Gene, CHL1. J. Biol. Chem. 272: 3823-3832 [Abstract] [Full Text]
Battistoni, A, Guarguaglini, G, Degrassi, F, Pittoggi, C, Palena, A, Di Matteo, G, Pisano, C, Cundari, E, Lavia, P (1997). Deregulated expression of the RanBP1 gene alters cell cycle progression in murine fibroblasts. J. Cell Sci. 110: 2345-2357 [Abstract]
Saredi, A, Howard, L, Compton, D. (1997). Phosphorylation regulates the assembly of NuMA in a mammalian mitotic extract. J. Cell Sci. 110: 1287-1297 [Abstract]
Saredi, A., Howard, L., Compton, D. A. (1996). NuMA assembles into an extensive filamentous structure when expressed in the cell cytoplasm. J. Cell Sci. 109: 619-630 [Abstract]
Hsu, H., Yeh, N. (1996). Dynamic changes of NuMA during the cell cycle and possible appearance of a truncated form of NuMA during apoptosis. J. Cell Sci. 109: 277-288 [Abstract]
Weaver, V., Carson, C., Walker, P., Chaly, N, Lach, B, Raymond, Y, Brown, D., Sikorska, M (1996). Degradation of nuclear matrix and DNA cleavage in apoptotic thymocytes. J. Cell Sci. 109: 45-56 [Abstract]
Trump, B. F. (1995). Mechanisms of Toxicity and Carcinogenesis. Toxicol Pathol 23: 775-827
Takahashi, K., Paladini, R. D., Coulombe, P. A. (1995). Cloning and Characterization of Multiple Human Genes and cDNAs Encoding Highly Related Type II Keratin 6 Isoforms. J. Biol. Chem. 270: 18581-18592 [Abstract] [Full Text]
Whitfield, W., Chaplin, M., Oegema, K, Parry, H, Glover, D. (1995). The 190 kDa centrosome-associated protein of Drosophila melanogaster contains four zinc finger motifs and binds to specific sites on polytene chromosomes. J. Cell Sci. 108: 3377-3387 [Abstract]
Compton, D., Luo, C (1995). Mutation of the predicted p34cdc2 phosphorylation sites in NuMA impair the assembly of the mitotic spindle and block mitosis. J. Cell Sci. 108: 621-633 [Abstract]
Tang, T., Tang, C., Chao, Y., Wu, C. (1994). Nuclear mitotic apparatus protein (NuMA): spindle association, nuclear targeting and differential subcellular localization of various NuMA isoforms. J. Cell Sci. 107: 1389-1402 [Abstract]
Barthelmes, H. U., Grue, P., Feineis, S., Straub, T., Boege, F. (2000). Active DNA Topoisomerase IIalpha Is a Component of the Salt-stable Centrosome Core. J. Biol. Chem. 275: 38823-38830 [Abstract] [Full Text]
Mack, G. J., Compton, D. A. (2001). Analysis of mitotic microtubule-associated proteins using mass spectrometry identifies astrin, a spindle-associated protein. Proc. Natl. Acad. Sci. USA 98: 14434-14439 [Abstract] [Full Text]