Alternative titles; symbols
HGNC Approved Gene Symbol: ZW10
Cytogenetic location: 11q23.2 Genomic coordinates (GRCh38) : 11:113,733,187-113,773,692 (from NCBI)
Mutations in the Drosophila zeste-white 10 (zw10) gene disrupt chromosome segregation, producing chromosomes that lag at the metaphase plate during anaphase of mitosis and both meiotic divisions. During the cell cycle, the Drosophila zw10 protein moves from the centromere/kinetochore at prometaphase to kinetochore microtubules at metaphase, and then back to the centromere/kinetochore at anaphase. Starr et al. (1997) suggested that zw10 may act at the kinetochore as part of a tension-sensing checkpoint that renders anaphase onset dependent upon bipolar tension exerted across all centromeres. By screening an EST database, they identified cDNAs encoding zw10 homologs in organisms with divergent centromere structures, including human, C. elegans, and Arabidopsis. Overall, the predicted ZW10 proteins of Drosophila, C. elegans, human, and Arabidopsis share 17 to 26% identity. Northern blot analysis revealed that the human ZW10 gene was expressed as an approximately 2.9-kb mRNA in various human cell lines. On Western blots of HeLa cell extracts, the deduced 779-amino acid human ZW10 protein migrated as a doublet of approximately 90 kD. Using immunofluorescence, the authors determined that ZW10 displayed a dynamic pattern of localization during the HeLa cell cycle, similar to that observed for Drosophila zw10.
Starr et al. (1997) found that injection of antisense C. elegans zw10 RNA into nematode gonads caused cell division disruptions similar to those seen in Drosophila zw10 mutants. They concluded that at least some aspects of the functional role of the ZW10 protein in ensuring proper chromosome segregation are conserved in higher eukaryotes.
By coimmunoprecipitation of HeLa cells, Chan et al. (2000) and Scaerou et al. (2001) determined that KNTC1 (607363) interacts with ZW10. Using a yeast 2-hybrid screen, Scaerou et al. (2001) localized the ZW10-binding region to the middle third of KNTC1. By immunofluorescent localization in synchronized HeLa cells, Scaerou et al. (2001) found KNTC1 and ZW10 colocalized at kinetochores during prometaphase and metaphase, with the brightest staining for both proteins on the spindle near the poles. After late anaphase and telophase, ZW10 accumulated at the spindle midzone, while KNTC1 staining became prominent at the spindle poles. By injection of antibodies directed toward KNTC1 or ZW10 into HeLa cells shortly after their release from the G1/S boundary, Chan et al. (2000) found that anaphase cells contained lagging chromosomes and divided cells contained chromatin bridges. They concluded that both KNTC1 and ZW10 are essential components of the mitotic checkpoint.
Using yeast 2-hybrid analysis, Starr et al. (2000) demonstrated a direct interaction between ZWINT (609177) and ZW10. The C-terminal third of ZW10 interacted with ZWINT, but the full-length protein showed a tighter association. At prophase, ZWINT localized to the kinetochore prior to ZW10 localization. Starr et al. (2000) hypothesized that ZWINT may play a role in targeting ZW10 to the kinetochore at prometaphase.
Musio et al. (2004) found that inhibition of INCENP (604411), ZWINT, and ZW10 with antisense oligonucleotides resulted in the appearance of mitotic cells characterized by centromere separation, chromosome aneuploidy, and micronuclei formation. The chromosome morphology was similar to that of Roberts syndrome (268300) chromosomes when analyzed by atomic force microscopy.
The International Radiation Hybrid Mapping Consortium mapped the ZW10 gene to chromosome 11 (RH12322).
Chan, G. K. T., Jablonski, S. A., Starr, D. A., Goldberg, M. L., Yen, T. J. Human Zw10 and ROD are mitotic checkpoint proteins that bind to kinetochores. Nature Cell Biol. 2: 944-947, 2000. [PubMed: 11146660] [Full Text: https://doi.org/10.1038/35046598]
Musio, A., Mariani, T., Montagna, C., Zambroni, D., Ascoli, C., Ried, T., Vezzoni, P. Recapitulation of the Roberts syndrome cellular phenotype by inhibition of INCENP, ZWINT-1 and ZW10 genes. Gene 331: 33-40, 2004. [PubMed: 15094189] [Full Text: https://doi.org/10.1016/j.gene.2004.01.028]
Scaerou, F., Starr, D. A., Piano, F., Papoulas, O., Karess, R. E., Goldberg, M. L. The ZW10 and rough deal checkpoint proteins function together in a large, evolutionarily conserved complex targeted to the kinetochore. J. Cell Sci. 114: 3103-3114, 2001. [PubMed: 11590237] [Full Text: https://doi.org/10.1242/jcs.114.17.3103]
Starr, D. A., Saffery, R., Li, Z., Simpson, A. E., Choo, K. H. A., Yen, T. J., Goldberg, M. L. HZwint-1, a novel human kinetochore component that interacts with HZW10. J. Cell Sci. 113: 1939-1950, 2000. [PubMed: 10806105] [Full Text: https://doi.org/10.1242/jcs.113.11.1939]
Starr, D. A., Williams, B. C., Li, Z., Etemad-Moghadam, B., Dawe, R. K., Goldberg, M. L. Conservation of the centromere/kinetochore protein ZW10. J. Cell Biol. 138: 1289-1301, 1997. [PubMed: 9298984] [Full Text: https://doi.org/10.1083/jcb.138.6.1289]