Loss of function of the Cik1/Kar3 motor complex results in chromosomes with syntelic attachment that are sensed by the tension checkpoint.
Loss of function of the Cik1/Kar3 motor complex results in chromosomes with syntelic attachment that are sensed by the tension checkpoint.
复制标题
DOI：
10.1371/journal.pgen.1002492
复制
发表时间：
2012-02
期刊：
影响因子：
4.5
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Jin F;Liu H;Li P;Yu HG;Wang Y
姐妹着丝点通过来自相反纺锤体两极的微管附着，形成染色体两极附着，对染色体产生张力，是姐妹染色单体分离所必需的。当姐妹着丝点通过同一纺锤体极上的微管附着，这种附着不能在染色体上产生张力时，就会发生联体附着，但在萌芽酵母中没有可靠的方法来诱导联体附着。纺锤体检查点可以感觉到染色体上缺乏张力，以及分离的动粒，以防止后期开始。在萌芽酵母中，张力检查点蛋白Aurora/Ipl1激酶和着丝粒定位的Sgo1是感受张力缺失所必需的，但对于检验点对分离的动粒的反应是必不可少的。我们已经发现，在萌芽酵母中，运动蛋白复合体Cik1/Kar3功能的丧失会导致联结附着。纺锤体或张力检查点的失活使带有功能障碍的Cik1/Kar3的细胞提前进入后期，导致姐妹染色单体的共同分离。此外，cik1突变体中取消的Kar3-动粒相互作用表明，Cik1/Kar3复合体介导了染色体沿微管的移动，这可能有助于双极附着。因此，我们可以通过失活Cik1/Kar3复合体来诱导发芽酵母发生联会附着，这一方法将对研究联会附着的检查点反应非常有用。当姐妹染色单体被从相反纺锤体两极发出的微管连接时，染色体两极附着发生，这对于忠实的姐妹染色单体分离是必不可少的。一旦两极连接建立，染色体就处于紧张状态。张力检查点通过防止染色体分离的张力检查点来感觉到没有张力。姐妹染色单体通过来自同一纺锤体极的微管附着产生联会附着，而不会在染色体上产生张力。然而，目前还没有一种可靠的方法来诱导联觉依恋。我们的发现表明，在萌芽酵母中，运动复合体Cik1/Kar3的失活导致了染色体的同义附着。在没有张力检查点的情况下，带有功能失调的Cik1/Kar3的酵母细胞进入后期，导致姐妹染色单体的共同分离。因此，使用这种方法，我们可以在实验中诱导酵母中的联体附着，并研究细胞如何对这种错误的附着做出反应。
The attachment of sister kinetochores by microtubules emanating from opposite spindle poles establishes chromosome bipolar attachment, which generates tension on chromosomes and is essential for sister-chromatid segregation. Syntelic attachment occurs when both sister kinetochores are attached by microtubules from the same spindle pole and this attachment is unable to generate tension on chromosomes, but a reliable method to induce syntelic attachments is not available in budding yeast. The spindle checkpoint can sense the lack of tension on chromosomes as well as detached kinetochores to prevent anaphase onset. In budding yeast Saccharomyces cerevisiae, tension checkpoint proteins Aurora/Ipl1 kinase and centromere-localized Sgo1 are required to sense the absence of tension but are dispensable for the checkpoint response to detached kinetochores. We have found that the loss of function of a motor protein complex Cik1/Kar3 in budding yeast leads to syntelic attachments. Inactivation of either the spindle or tension checkpoint enables premature anaphase entry in cells with dysfunctional Cik1/Kar3, resulting in co-segregation of sister chromatids. Moreover, the abolished Kar3-kinetochore interaction in cik1 mutants suggests that the Cik1/Kar3 complex mediates chromosome movement along microtubules, which could facilitate bipolar attachment. Therefore, we can induce syntelic attachments in budding yeast by inactivating the Cik1/Kar3 complex, and this approach will be very useful to study the checkpoint response to syntelic attachments. Chromosome bipolar attachment occurs when sister chromatids are attached by microtubules emanating from opposite spindle poles and is essential for faithful sister-chromatid segregation. Chromosomes are under tension once bipolar attachment is established. The absence of tension is sensed by the tension checkpoint that prevents chromosome segregation. The attachment of sister chromatids by microtubules from the same spindle pole generates syntelic attachment, which fails to generate tension on chromosomes. However, a reliable method to induce syntelic attachment is not available. Our findings indicate that the inactivation of the motor complex, Cik1/Kar3, results in chromosomes with syntelic attachment in budding yeast. In the absence of the tension checkpoint, yeast cells with dysfunctional Cik1/Kar3 enter anaphase, resulting in co-segregation of sister chromatids. Therefore, with this method we can experimentally induce syntelic attachment in yeast and investigate how cells respond to this incorrect attachment.
登录
查看更多内容
影响因子：
16
作者：
Benanti, Jennifer A.;Matyskiela, Mary E.;Toczyski, David P.
通讯作者：
Toczyski, David P.
影响因子：
10.5
作者：
CohenFix, O;Peters, JM;Koshland, D
通讯作者：
Koshland, D
影响因子：
64.5
作者：
Ciosk, R;Zachariae, W;Nasmyth, K
通讯作者：
Nasmyth, K
影响因子：
3.3
作者：
Jones, MH;Bachant, JB;Winey, M
通讯作者：
Winey, M
影响因子：
3.3
作者：
Barrett, JG;Manning, BD;Snyder, M
通讯作者：
Snyder, M