CONSERVATION OF THE CENTROMERE KINETOCHORE PROTEIN ZW10/

Mutations in the essential Drosophila melanogaster gene zw10 disrupt c hromosome segregation, producing chromosomes that lag at the metaphase plate during anaphase of mitosis and both meiotic divisions. Recent e vidence suggests that the product of this gene, DmZW10, acts at the ki netochore as part of a tension-sensing checkpoint at anaphase onset. D mZW10 displays an intriguing cell cycle-dependent intracellular distri bution, apparently moving from the centromere/kinetochore at prometaph ase to kinetochore microtubules at metaphase, and back to the centrome re/kinetochore at anaphase (Williams, B.C., M. Gatti, and M.L. Goldber g. 1996. J. Cell Biol. 134:1127-1140). We have identified ZW10-related proteins from widely diverse species with divergent centromere struct ures, including several Drosophilids, Caenorhabditis elegans, Arabidop sis thaliana, Mus musculus, and humans. Antibodies against the human Z W10 protein display a cell cycle-dependent staining pattern in HeLa ce lls strikingly similar to that, previously observed for DmZW10 in divi ding Drosophila cells. Injections of C. elegans ZW10 antisense RNA phe nocopies important aspects of the mutant phenotype in Drosophila: thes e include a strong decrease in brood size, suggesting defects in meios is or germline mitosis, a high percentage of lethality among the embry os that are produced, and the appearance of chromatin bridges at anaph ase. These results indicate that at least some aspects of the function al role of the ZW10 protein in ensuring proper chromosome segregation are conserved across large evolutionary distances.