Rae1 is an essential mitotic checkpoint regulator that cooperates with Bub3 to prevent chromosome missegregation.
Rae1 is an essential mitotic checkpoint regulator that cooperates with Bub3 to prevent chromosome missegregation.
复制标题
DOI：
10.1083/jcb.200211048
复制
发表时间：
2003-02-03
期刊：
影响因子：
--
通讯作者：
van Deursen JM
中科院分区：
文献类型：
--
作者：
Babu JR;Jeganathan KB;Baker DJ;Wu X;Kang-Decker N;van Deursen JM
WD重复蛋白Rae1和Bub3显示出广泛的序列同源性，这表明它们具有功能相似性。然而，先前的研究表明，Rae1参与mRNA输出途径，而Bub3参与有丝分裂检查点。为了确定Rae1和Bub3在哺乳动物体内的作用，我们构建了单独或联合缺失这些基因的基因敲除小鼠。在此我们表明，Rae1或Bub3的单倍体不足都会导致一种相似的表型，涉及有丝分裂检查点缺陷和染色体错误分离。我们还表明，Rae1的过表达可以纠正Rae1单倍体不足，并且令人惊讶的是，也能纠正Bub3单倍体不足。Rae1基因缺失和Bub3基因缺失的小鼠在胚胎期是致死的，尽管来自这些小鼠的细胞在mRNA的核输出方面没有可检测到的缺陷。与基因缺失小鼠不同，复合单倍体不足的Rae1/Bub3小鼠是存活的。然而，来自这些小鼠的细胞比单一单倍体不足的细胞表现出更高的早熟姐妹染色单体分离和染色体错误分离的比率。最后，我们表明，具有有丝分裂检查点缺陷的小鼠比野生型小鼠更容易受到二甲基苯并蒽诱导的肿瘤发生的影响。因此，我们的数据证明了Rae1的一种新功能，并将Rae1和Bub3描述为在有丝分裂检查点中具有关键、重叠和协同作用的相关蛋白。
The WD-repeat proteins Rae1 and Bub3 show extensive sequence homology, indicative of functional similarity. However, previous studies have suggested that Rae1 is involved in the mRNA export pathway and Bub3 in the mitotic checkpoint. To determine the in vivo roles of Rae1 and Bub3 in mammals, we generated knockout mice that have these genes deleted individually or in combination. Here we show that haplo-insufficiency of either Rae1 or Bub3 results in a similar phenotype involving mitotic checkpoint defects and chromosome missegregation. We also show that overexpression of Rae1 can correct for Rae1 haplo-insufficiency and, surprisingly, Bub3 haplo-insufficiency. Rae1-null and Bub3-null mice are embryonic lethal, although cells from these mice did not have a detectable defect in nuclear export of mRNA. Unlike null mice, compound haplo-insufficient Rae1/Bub3 mice are viable. However, cells from these mice exhibit much greater rates of premature sister chromatid separation and chromosome missegregation than single haplo-insufficient cells. Finally, we show that mice with mitotic checkpoint defects are more susceptible to dimethylbenzanthrene-induced tumorigenesis than wild-type mice. Thus, our data demonstrate a novel function for Rae1 and characterize Rae1 and Bub3 as related proteins with essential, overlapping, and cooperating roles in the mitotic checkpoint.
登录
查看更多内容
影响因子：
11.4
作者：
Braun, IC;Rohrbach, E;Izaurralde, E
通讯作者：
Izaurralde, E
影响因子：
64.8
作者：
Cahill, DP;Lengauer, C;Vogelstein, B
通讯作者：
Vogelstein, B
DOI：
10.1073/pnas.94.17.9119
发表时间：
1997-08-19
影响因子：
11.1
作者：
Kraemer, D;Blobel, G
通讯作者：
Blobel, G
影响因子：
10.5
作者：
Kalitsis, P;Earle, E;Choo, KHA
通讯作者：
Choo, KHA
影响因子：
11.4
作者：
Cheng, MG;Olivier, P;Sherr, CJ
通讯作者：
Sherr, CJ