Identification of a human mitotic checkpoint gene: hsMAD2.
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.
Li
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Cell Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Benezra
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D000595:Amino Acid Sequence; D000705:Anaphase; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D018797:Cell Cycle Proteins; D018274:Electroporation; D006367:HeLa Cells; D006801:Humans; D007399:Interphase; D018386:Kinetochores / Q000378:metabolism*; D064246:Mad2 Proteins; D008677:Metaphase; D008938:Mitosis; D008969:Molecular Sequence Data; D015739:Nocodazole / Q000494:pharmacology; D017239:Paclitaxel / Q000494:pharmacology; D012097:Repressor Proteins; D008941:Spindle Apparatus / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D012097:Repressor Proteins; D017239:Paclitaxel; D015739:Nocodazole