title: Caspase-3-mediated degradation of condensin Cap-H regulates mitotic cell death.
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.
authors.affiliation: Division of Molecular and Cell Biology, School of Biological Sciences, College of Science, Nanyang Technological University, Singapore, Singapore.
authors.forename: S-K
authors.initials: SK
authors.lastname: Lai
authors.forename: C-H
authors.initials: CH
authors.lastname: Wong
authors.forename: Y-P
authors.initials: YP
authors.lastname: Lee
authors.forename: H-Y
authors.initials: HY
authors.lastname: Li
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D016923:Cell Death / Q000235:genetics; D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism*; D053938:DNA Fragmentation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D046912:Multiprotein Complexes; C108312:condensin complexes; C505407:CASP3 protein, human; D053148:Caspase 3; D000251:Adenosine Triphosphatases