Mitotic arrest: Mad2 prevents sleepy from waking up the APC
Mitotic arrest: Mad2 prevents sleepy from waking up the APC
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DOI：
10.1126/science.279.5353.999
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发表时间：
1998-02-13
期刊：
影响因子：
56.9
通讯作者：
Elledge, SJ
中科院分区：
文献类型：
--
作者：
Elledge, SJ
植物和动物要生长，它们的细胞必须自我复制。这些细胞必须精确地复制它们的染色体，并通过有丝分裂的过程，将它们分离成子细胞。不能成功地将新染色体传递给后代是灾难性的，产生的细胞染色体太少或太多（非整倍体），导致细胞死亡、出生缺陷或癌症。细胞避免这种灾难的一种方法是通过称为纺锤体组装检查点的监视机制(1)。这条途径监测有丝分裂纺锤体，一种双极微管阵列，附着在染色体的一个特殊区域（着丝点），最终将复制的染色体（姐妹染色单体）分开。检查点阻止姐妹染色单体分离（后期），直到两个姐妹连接到纺锤体的相反极点，从而确保染色体在子细胞中的均匀分布。（参见1月23日《科学》杂志第477页的相关新闻报道。）1991年，在出芽酵母中发现了MAD（有丝分裂阻滞缺陷）和BUB（不受苯并咪唑抑制的出芽）基因，这一途径获得了分子基础（2,3）。Mad和Bub蛋白感知染色体位置和纺锤体附着，并将这些信息传递给基本的细胞周期机制。Mad2和Bub1存在于未附着的着丝点上，为细胞生物学实验提供了分子联系，这些实验表明检查点检测到尚未与微管相互作用的着丝点（4-6）。
For plants and animals to grow, their cells must duplicate themselves. These cells must accurately copy their chromosomes and, through the process of mitosis, segregate them to daughter cells. Failure to deliver the new chromosomes successfully to offspring is disastrous, producing cells with too few or too many chromosomes (aneuploidy), resulting in cell death, birth defects, or cancer. One way that cells avoid this calamity is through a surveillance mechanism called the spindle assembly checkpoint (1). This pathway monitors the mitotic spindle, a bipolar array of microtubules that attach to a specialized region of the chromosome (the kinetochore), eventually pulling apart the replicated chromosomes (sister chromatids). The checkpoint blocks sister chromatid separation (anaphase) until the two sisters are attached to opposite poles of the spindle and thus ensures equal distribution of chromosomes into daughter cells.(See the related News story on page 477 of the 23 January issue of Science.)This pathway gained a molecular footing in 1991 with the identification of the MAD (mitotis arrest deficient) and BUB (budding uninhibited by benzimidazole) genes in budding yeast (2, 3). The Mad and Bub proteins sense chromosome position and spindle attachment and transduce this information to the basic cell cycle machinery. Mad2 and Bub1 are found on unattached kinetochores, providing a molecular link to cell biological experiments that suggest that the checkpoint detects kinetochores that have not yet interacted with microtubules (4–6).