期刊
JOURNAL OF CELL BIOLOGY
卷 164, 期 4, 页码 535-546出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200308100
关键词
chromosome segregation; kinetochores; mitotic spindle apparatus; mitosis; metaphase
类别
资金
- NCI NIH HHS [R01 CA084179, CA84179] Funding Source: Medline
- NIGMS NIH HHS [R01 GM051464, GM51464] Funding Source: Medline
Accurate chromosome segregation depends on precise regulation of mitosis by the spindle checkpoint. This checkpoint monitors the status of kinetochoremicrotubule attachment and delays the metaphase to anaphase transition until all kinetochores have formed stable bipolar connections to the mitotic spindle. Components of the spindle checkpoint include the mitotic arrest defective (MAD) genes MAD1-3, and the budding uninhibited by benzimidazole (BUB) genes BUB1 and BUB3. In animal cells, all known spindle checkpoint proteins are recruited to kinetochores during normal mitoses. In contrast, we show that whereas Saccharomyces cerevisiae Bub1p and Bub3p are bound to kinetochores early in mitosis as part of the normal cell cycle, Mad1p and Mad2p are kinetochore bound only in the presence of spindle damage or kinetochore lesions that interfere with chromosome-microtubule attachment. Moreover, although Mad1p and Mad2p perform essential mitotic functions during every division cycle in mammalian cells, they are required in budding yeast only when mitosis goes awry. We propose that differences in the behavior of spindle checkpoint proteins in animal cells and budding yeast result primarily from evolutionary divergence in spindle assembly pathways.
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