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Science 11 October 1996:
Vol. 274. no. 5285, pp. 246 - 248
DOI: 10.1126/science.274.5285.246
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Reports

Identification of a Human Mitotic Checkpoint Gene: hsMAD2

Yong Li and Robert Benezra *

In Saccharomyces cerevisiae, MAD2 is required for mitotic arrest if the spindle assembly is perturbed. The human homolog of MAD2 was isolated and shown to be a necessary component of the mitotic checkpoint in HeLa cells by antibody electroporation experiments. Human, or Homo sapiens, MAD2 (hsMAD2) was localized at the kinetochore after chromosome condensation but was no longer observed at the kinetochore in metaphase, suggesting that MAD2 might monitor the completeness of the spindle-kinetochore attachment. Finally, T47D, a human breast tumor cell line that is sensitive to taxol and nocodazole, had reduced MAD2 expression and failed to arrest in mitosis after nocodazole treatment. Thus, defects in the mitotic checkpoint may contribute to the sensitivity of certain tumors to mitotic spindle inhibitors.

Cell Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
*   To whom correspondence should be addressed.

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Probing Spindle Assembly Mechanisms with Monastrol, a Small Molecule Inhibitor of the Mitotic Kinesin, Eg5.
T. M. Kapoor, T. U. Mayer, M. L. Coughlin, and T. J. Mitchison (2000)
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Genomic Instability at the BUB1 Locus in Colorectal Cancer, but not in Non-Small Cell Lung Cancer1.
R. G. Jaffrey, S. C. Pritchard, C. Clark, G. I. Murray, J. Cassidy, K. M. Kerr, M. C. Nicolson, and H. L. McLeod (2000)
Cancer Res. 60, 4349-4352
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Interphase-specific association of intrinsic centromere protein CENP-C with HDaxx, a death domain-binding protein implicated in Fas-mediated cell death.
A. Pluta, W. Earnshaw, and I. Goldberg (2000)
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MAD3 Encodes a Novel Component of the Spindle Checkpoint Which Interacts with Bub3p, Cdc20p, and Mad2p.
K. G. Hardwick, R. C. Johnston, D. L. Smith, and A. W. Murray (2000)
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A Human REV7 Homolog That Interacts with the Polymerase zeta Catalytic Subunit hREV3 and the Spindle Assembly Checkpoint Protein hMAD2.
Y. Murakumo, T. Roth, H. Ishii, D. Rasio, S.-i. Numata, C. M. Croce, and R. Fishel (2000)
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Mitotic phosphorylation of SUV39H1, a novel component of active centromeres, coincides with transient accumulation at mammalian centromeres.
L Aagaard, M Schmid, P Warburton, and T Jenuwein (2000)
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Mitotic Checkpoints, Genetic Instability, and Cancer.
M. DOBLES and P.K. SORGER (2000)
Cold Spring Harb Symp Quant Biol 65, 361-368
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Protein dynamics at the kinetochore: cell cycle regulation of the metaphase to anaphase transition.
G. J. GORBSKY, M. KALLIO, J. R. DAUM, and L. M. TOPPER (1999)
FASEB J 13, 231S-234S
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BUBR1 Phosphorylation Is Regulated during Mitotic Checkpoint Activation.
W. Li, Z. Lan, H. Wu, S. Wu, J. Meadows, J. Chen, V. Zhu, and W. Dai (1999)
Cell Growth Differ. 10, 769-775
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Discovery of Differentially Expressed Genes Associated with Paclitaxel Resistance Using cDNA Array Technology: Analysis of Interleukin (IL) 6, IL-8, and Monocyte Chemotactic Protein 1 in the Paclitaxel-resistant Phenotype.
Z. Duan, A. J. Feller, R. T. Penson, Bruce. A. Chabner, and M. V. Seiden (1999)
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