Selective proteolysis of the nuclear replication factor MCM3 in apoptosis

Cleavage of specific protein subsets is a key event in the execution of apoptosis. Protein degradation may serve for the structural alterations that result in cell self-destruction, but it may also function as a switch in the decisions between apoptosis and necrosis or apoptosis and cell proliferation. Here, we show that MCM3, but not other members of the Mcm family of replicative proteins, is cleaved early in several models of apoptosis. Cleavage of MCM3 can be prevented by caspase inhibitors, and it does not occur when cells are forced to undergo necrosis by energy deprivation. We propose that active destruction of MCM3 inactivates the Mcm complex and serves to prevent untimely DNA replication events during the execution of the cell death program.