Abstract
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.
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Abbreviations
- CAD:
-
caspase-activated DNase
- EGFP:
-
enhanced green fluorescent protein
- FACS:
-
Fluorescence-activated cell sorting
- ICAD:
-
inhibitor of CAD
- SEM:
-
scanning electron microscopy
- SMC:
-
structural maintenance of chromosome
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Acknowledgements
We thank Carl Zeiss Advanced Imaging Centre Singapore for technical assistance with scanning electron microscopy. This work was supported by Academic Research Council, Ministry of Education, Singapore (Academic Research Fund AcRF Tier 1, RG37/08) and A*STAR, Biomedical Research Council (BMRC grant 08/1/22/19/568).
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Lai, SK., Wong, CH., Lee, YP. et al. Caspase-3-mediated degradation of condensin Cap-H regulates mitotic cell death. Cell Death Differ 18, 996–1004 (2011). https://doi.org/10.1038/cdd.2010.165
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DOI: https://doi.org/10.1038/cdd.2010.165
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