The C-terminal helix of BubR1 is essential for CENP-E-dependent chromosome alignment
The C-terminal helix of BubR1 is essential for CENP-E-dependent chromosome alignment
复制标题
DOI：
10.1242/jcs.246025
复制
发表时间：
2020-08-01
影响因子：
4
通讯作者：
Welburn, Julie P. I.
中科院分区：
文献类型：
--
作者：
Legal, Thibault;Hayward, Daniel;Welburn, Julie P. I.
在细胞分裂过程中，未对齐的染色体在分离之前被马达捕获并对齐。CENP-E马达被募集到极性未连接的动粒以促进染色体对齐。纺锤体检查点蛋白BubR 1（也称为BUB 1B）已被报道为CENP-E相互作用伴侣，但BubR 1在多大程度上有助于CENP-E定位在着丝粒上仍然存在争议。在这里，我们定义的分子决定因素，指定BubR 1和CENP-E之间的相互作用。BubR 1的基本C-末端螺旋对于CENP-E相互作用是必需的，但不是充分的，并且CENP-E的激动素靶向结构域上的最小关键酸性补丁也是必需的。然后，我们证明，BubR 1是所需的招聘CENPE着丝粒，以促进染色体对齐。BubR 1-CENP-E轴对于未能通过其他途径进行国会的染色体的对齐至关重要，并概括了CENP-E的主要已知功能。总之，我们的研究确定了哺乳动物有丝分裂过程中CENP-E在着丝粒上募集到BubR 1的分子基础和功能。
During cell division, misaligned chromosomes are captured and aligned by motors before their segregation. The CENP-E motor is recruited to polar unattached kinetochores to facilitate chromosome alignment. The spindle checkpoint protein BubR1 (also known as BUB1B) has been reported as a CENP-E interacting partner, but the extent to which BubR1 contributes to CENP-E localization at kinetochores has remained controversial. Here we define the molecular determinants that specify the interaction between BubR1 and CENP-E. The basic C-terminal helix of BubR1 is necessary but not sufficient for CENP-E interaction, and a minimal key acidic patch on the kinetochore-targeting domain of CENP-E is also essential. We then demonstrate that BubR1 is required for the recruitment of CENPE to kinetochores to facilitate chromosome alignment. This BubR1-CENP-E axis is critical for alignment of chromosomes that have failed to congress through other pathways and recapitulates the major known function of CENP-E. Overall, our studies define the molecular basis and the function for CENP-E recruitment to BubR1 at kinetochores during mammalian mitosis.This article has an associated First Person interview with the first author of the paper.