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.
