Steigemann Patrick, Wurzenberger Claudia, Schmitz Michael H A, Held Michael, Guizetti Julien, Maar Sandra, Gerlich Daniel W
Institute of Biochemistry, Swiss Institute of Technology Zurich, ETHZ, Zurich, Switzerland.
Cell. 2009 Feb 6;136(3):473-84. doi: 10.1016/j.cell.2008.12.020.
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.
基因组异常在肿瘤细胞中经常可见，而由胞质分裂过程中的失败导致的四倍体化被认为是癌症形成的早期步骤。在此，我们报告一种细胞分裂控制机制，该机制可防止染色体分离受到干扰的人类细胞发生四倍体化。首先，我们发现极光激酶B（Aurora B）失活通过切割促进胞质分裂的完成。染色体桥使极光激酶B的活性持续到末期后阶段，从而延迟了稳定的细胞间通道处的切割。这对于通过进一步涉及有丝分裂驱动蛋白样蛋白1（Mklp1）磷酸化的途径抑制沟回退导致的四倍体化至关重要。我们提出极光激酶B是一种传感器的一部分，该传感器可对切割位点处未分离的染色质做出反应。我们的研究提供了证据，表明在人类细胞中，切割与染色体分离的完成相协调，以防止沟回退导致的四倍体化。
