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Components of the spindle-assembly checkpoint are essential in Caenorhabditis elegans

Nature Cell Biology volume 1, pages 514–521 (1999)Cite this article

Abstract

The spindle-assembly checkpoint ensures that, during mitosis and meiosis, chromosomes do not segregate until they are properly attached to the microtubules of the spindle. Here we show that mdf-1 and mdf-2 are components of the spindle-assembly checkpoint in Caenorhabditis elegans, and are essential for the long-term survival and fertility of this organism. Loss of function of either of these genes leads to the accumulation of a variety of defects, including chromosome abnormalities, X-chromosome non-disjunction or loss, problems in gonad development, and embryonic lethality. Antibodies that recognize the MDF-2 protein localize to nuclei of the cleaving embryo in a cell-cycle-dependent manner. mdf-1, a gene encoding a product that interacts with MDF-2, is required for cell-cycle arrest and proper chromosome segregation in premeiotic germ cells treated with nocodoazole, a microtubule-depolymerizing agent. In the absence of mdf gene products, errors in chromosome segregation arise and accumulate, ultimately leading to genetic lethality.

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Figure 1: mdf-2 rescues the benomyl sensitivity of mad2 mutants.
Figure 2: Subcellular localization of MDF-2 in mitotically dividing early embryonic cells.
Figure 3: Distribution of MDF-2 in late-stage embryos and germ cells.
Figure 4: Subcellular localization of MDF-2 during meiosis I, meiosis II and meiotic metaphase.
Figure 5: Germline defects in mdf-1 homozygous and mdf-2 RNAi worms.
Figure 6: mdf-1 homozygous worms show defects in nocodazole-induced mitotic cell-cycle arrest.

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Acknowledgements

We thank P. Hieter, A. Murray, B. Nicklas, A. Page, D. Shakes and D. Baillie for discussion and comments on the manuscript. This research was supported by the Natural Sciences and Engineering Research Council of Canada and the British Columbia Health Research Foundation.

Correspondence and requests for materials should be addressed to A.M.R.

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  1. Department of Medical Genetics, University of British Columbia, 6174 University Boulevard, Vancouver, V6T 1Z3, British Columbia, Canada

    Risa Kitagawa & Ann M. Rose

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Correspondence to Ann M. Rose.

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Kitagawa, R., Rose, A. Components of the spindle-assembly checkpoint are essential in Caenorhabditis elegans. Nat Cell Biol 1, 514–521 (1999). https://doi.org/10.1038/70309

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