Caspase-mediated degradation of condensin I CAP-H during mitotic catastrophe.

Abstract

Mitotic catastrophe is a type of cell death that occurs after failed mitosis. However, little is known about the mechanism underlying this form of cell death. Previous studies have demonstrated that the protein level of CAP-H is reduced during taxol-induced mitotic catastrophe. Depletion of CAP-H resulted in the loss of condensin I from mitotic chromosomes, weakening chromosome integrity. Consequently, chromosome fragmentation is facilitated, leading to cell death by mitotic catastrophe. Here, we proposed that the depletion of CAP-H is a result of caspase-3 activation during taxol-induced mitotic catastrophe. To verify this, polymerase chain reaction site-directed mutagenesis was performed to identify specific caspase cleavage sites in CAP-H. Six mutants have been successfully cloned and further studies are required to confirm that CAP-H is a substrate of activated caspase-3.