Division of Molecular and Cell Biology, School of Biological Sciences, College of Science, Nanyang Technological University, Singapore, Singapore.
Cell Death Differ. 2011 Jun;18(6):996-1004. doi: 10.1038/cdd.2010.165. Epub 2010 Dec 10.
Mitotic death is a major form of cell death in cancer cells that have been treated with chemotherapeutic drugs. However, the mechanisms underlying this form of cell death is poorly understood. Here, we report that the loss of chromosome integrity is an important determinant of mitotic death. During prolonged mitotic arrest, caspase-3 is activated and it cleaves Cap-H, a subunit of condensin I. The depletion of Cap-H results in the loss of condensin I complex at the chromosomes, thus affecting the integrity of the chromosomes. Consequently, DNA fragmentation by caspase-activated DNase is facilitated, thus driving the cell towards mitotic death. By expressing a caspase-resistant form of Cap-H, mitotic death is abrogated and the cells are able to reenter interphase after a long mitotic delay. Taken together, we provide new insights into the molecular events that occur during mitotic death.
有丝分裂死亡是癌细胞在接受化疗药物治疗后主要的细胞死亡形式。然而，这种细胞死亡形式的机制尚不清楚。在这里，我们报告染色体完整性的丧失是有丝分裂死亡的一个重要决定因素。在长时间的有丝分裂阻滞期间，半胱天冬酶-3 被激活，它切割着丝粒蛋白 H（Cap-H），这是凝缩素 I 的一个亚基。Cap-H 的耗竭导致着丝粒蛋白 I 复合物在染色体上的丢失，从而影响染色体的完整性。因此，被半胱天冬酶激活的 DNA 内切酶促进了 DNA 片段化，从而使细胞向有丝分裂死亡方向发展。通过表达半胱天冬酶抗性形式的 Cap-H，可以阻断有丝分裂死亡，并且细胞能够在长时间的有丝分裂延迟后重新进入细胞间期。总之，我们为有丝分裂死亡过程中发生的分子事件提供了新的见解。
