Rev7/Mad2B plays a critical role in the assembly of a functional mitotic spindle
Rev7/Mad2B plays a critical role in the assembly of a functional mitotic spindle
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DOI：
10.1080/15384101.2015.1120922
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发表时间：
2015-12-17
期刊：
影响因子：
4.3
通讯作者：
Xiao, Wei
中科院分区：
文献类型：
--
作者：
Bhat, Audesh;Wu, Zhaojia;Xiao, Wei
纺锤体组装检查点（SAC）作为一个卫士，防止可能导致染色体错分离和非整倍体的细胞威胁。Mad2是一种后期促进复合物/环体- cdc20 （APC/C-Cdc20）抑制剂，在哺乳动物中有另一种同源物，称为Mad2B， Mad2L2或Rev7。除了参与pol介导的翻译DNA合成和双链断裂修复外，Rev7还被认为通过负调控Cdh1抑制APC/C。在这里，我们报道了Rev7在培养的人类细胞中的另一种功能。如前所述，Rev7参与了纺锤体的形成和染色体分离的维持。在缺乏Rev7的情况下，细胞倾向于停留在G2/ m期，显示单星体增加和异常纺锤体，染色体排列不一致。此外，rev7缺失的细胞在中期细胞的着丝点显示出Mad2的定位，这是激活SAC的一个指标，同时APC（Cdc20）底物Cyclin B1水平升高。令人惊讶的是，与Mad2不同的是，在几种培养的人类细胞系中，Rev7的缺失并未损害SAC的活性。因此，我们的数据表明，除了在APC/C-Cdh1抑制中发挥作用外，Rev7也是有丝分裂纺锤体组织和忠实染色体分离所必需的，这很可能是通过它与RAN的物理相互作用。
The spindle assembly checkpoint (SAC) acts as a guardian against cellular threats that may lead to chromosomal missegregation and aneuploidy. Mad2, an anaphase-promoting complex/cyclosome-Cdc20 (APC/C-Cdc20) inhibitor, has an additional homolog in mammals known as Mad2B, Mad2L2 or Rev7. Apart from its role in Pol-mediated translesion DNA synthesis and double-strand break repair, Rev7 is also believed to inhibit APC/C by negatively regulating Cdh1. Here we report yet another function of Rev7 in cultured human cells. Rev7, as predicted earlier, is involved in the formation of a functional spindle and maintenance of chromosome segregation. In the absence of Rev7, cells tend to arrest in G2/M-phase and display increased monoastral and abnormal spindles with misaligned chromosomes. Furthermore, Rev7-depleted cells show Mad2 localization at the kinetochores of metaphase cells, an indicator of activated SAC, coupled with increased levels of Cyclin B1, an APC(Cdc20) substrate. Surprisingly unlike Mad2, depletion of Rev7 in several cultured human cell lines did not compromise SAC activity. Our data therefore suggest that besides its role in APC/C-Cdh1 inhibition, Rev7 is also required for mitotic spindle organization and faithful chromosome segregation most probably through its physical interaction with RAN.