Mad1 contribution to spindle assembly checkpoint signalling goes beyond presenting Mad2 at kinetochores
Mad1 contribution to spindle assembly checkpoint signalling goes beyond presenting Mad2 at kinetochores
复制标题
DOI：
10.1002/embr.201338114
复制
发表时间：
2014-03-01
期刊：
影响因子：
7.7
通讯作者：
Hauf, Silke
中科院分区：
文献类型：
--
作者：
Heinrich, Stephanie;Sewart, Katharina;Hauf, Silke
这项研究与Nilsson实验室的一项研究一起发表，表明仍然将Mad 2招募到着丝粒中的Mad 1突变体不能激活酵母中的纺锤体组装检查点。因此，Mad 1有一个额外的，迄今尚未确定的作用，在这个过程中。Mad 1的C-末端和Bub 1保守的基序1所需的着丝粒定位裂殖酵母Mad 1：Mad 2 complex。Mad 1的C-末端的“头”是必需的检查点活动，尽管是为Mad 1和Mad 2的着丝粒recruitment.Mad1是不只是提出Mad 2在着丝粒的支架，但它的C-末端另外促进checkpoint signaling.AbstractThe纺锤体组装checkpoint抑制后期，直到所有的染色体已经成为有丝分裂纺锤体连接。检查点蛋白Mad 1和Mad 2之间的复合物为Mad 2：Mad 2在未连接的动粒处的二聚化提供了平台，这使得Mad 2能够延迟后期。在这里，我们表明，Bub 1和Mad 1的C-末端结构域内的突变损害了Mad 1：Mad 2的动粒定位和废除检查点活性。在这些突变体中Mad 1的人工动粒招募共同招募Mad 2;然而，检查点仍然不起作用。我们确定了Mad 1的C-末端头部内的特定突变，这些突变损害检查点活性，而不影响Bub 1，Mad 1或Mad 2的动粒定位。因此，Mad 1可能与Bub 1结合，除了呈递Mad 2外，还在检查点信号传导中发挥关键作用。
SynopsisimageThis study, published alongside one from the Nilsson laboratory, shows that Mad1 mutants that still recruit Mad2 to kinetochores cannot activate the spindle assembly checkpoint in yeast. Thus, Mad1 has an additional, hitherto unidentified role in this process.The Mad1 C-terminus and Bub1 conserved motif 1 are required for kinetochore localization of the Schizosaccharomyces pombe Mad1:Mad2 complex.The Mad1 C-terminal "head" is required for checkpoint activity despite being dispensable for Mad1 and Mad2 kinetochore recruitment.Mad1 is not only the scaffold for presenting Mad2 at kinetochores, but its C-terminus additionally promotes checkpoint signalling.AbstractThe spindle assembly checkpoint inhibits anaphase until all chromosomes have become attached to the mitotic spindle. A complex between the checkpoint proteins Mad1 and Mad2 provides a platform for Mad2:Mad2 dimerization at unattached kinetochores, which enables Mad2 to delay anaphase. Here, we show that mutations in Bub1 and within the Mad1 C-terminal domain impair the kinetochore localization of Mad1:Mad2 and abrogate checkpoint activity. Artificial kinetochore recruitment of Mad1 in these mutants co-recruits Mad2; however, the checkpoint remains non-functional. We identify specific mutations within the C-terminal head of Mad1 that impair checkpoint activity without affecting the kinetochore localization of Bub1, Mad1 or Mad2. Hence, Mad1 potentially in conjunction with Bub1 has a crucial role in checkpoint signalling in addition to presenting Mad2.