Aurora B-Mediated Abscission Checkpoint Protects against Tetraploidization
Aurora B-Mediated Abscission Checkpoint Protects against Tetraploidization
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DOI：
10.1016/j.cell.2008.12.020
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发表时间：
2009-02-06
期刊：
影响因子：
64.5
通讯作者：
Gerlich, Daniel W.
中科院分区：
文献类型：
--
作者：
Steigemann, Patrick;Wurzenberger, Claudia;Gerlich, Daniel W.
肿瘤细胞中经常出现基因组异常，而胞质分裂过程失败导致的四倍体化被认为是癌症形成的早期步骤。在这里，我们报告了一种细胞分裂控制机制，可以防止染色体分离受到干扰的人类细胞四倍体化。首先，我们发现 Aurora B 失活可促进胞质分裂通过脱落完成。染色体桥将 Aurora B 活性维持到末期后阶段，从而延迟稳定细胞间管的脱落。这对于通过进一步涉及有丝分裂驱动蛋白样蛋白 1 (Mklp1) 磷酸化的途径中的沟道回归来抑制四倍体化至关重要。我们认为 Aurora B 是对切割位点未分离的染色质做出反应的传感器的一部分。我们的研究提供的证据表明，在人类细胞中，脱落与染色体分离的完成相协调，以防止皱纹回归引起的四倍体化。
Genomic abnormalities are often seen in tumor cells, and tetraploidization, which results from failures during cytokinesis, is presumed to be an early step in cancer formation. Here, we report a cell division control mechanism that prevents tetraploidization in human cells with perturbed chromosome segregation. First, we found that Aurora B inactivation promotes completion of cytokinesis by abscission. Chromosome bridges sustained Aurora B activity to posttelophase stages and thereby delayed abscission at stabilized intercellular canals. This was essential to suppress tetraploidization by furrow regression in a pathway further involving the phosphorylation of mitotic kinesin-like protein 1 (Mklp1). We propose that Aurora B is part of a sensor that responds to unsegregated chromatin at the cleavage site. Our study provides evidence that in human cells abscission is coordinated with the completion of chromosome segregation to protect against tetraploidization by furrow regression.