To study the role of caspase-6 during nuclear disassembly, we generated a 
chicken DT40 cell line in which both alleles of the caspase-6 gene were 
disrupted. No obvious morphological differences were observed in the apoptotic 
process in caspase-6- deficient cells compared with the wild type. However, 
examination of apoptosis in a cell-free system revealed a block in chromatin 
condensation and apoptotic body formation when nuclei from HeLa cells expressing 
lamin A or lamin A-transfected Jurkat cells were incubated in 
caspase-6-deficient apoptotic extracts. Transfection of exogenous caspase-6 into 
the clone reversed this phenotype. Lamins A and C, which are caspase-6-only 
substrates, were cleaved by the wild-type and heterozygous apoptotic extracts 
but not by the extracts lacking caspase-6. Furthermore, the caspase-6 inhibitor 
z-VEID-fmk mimicked the effects of caspase-6 deficiency and prevented the 
cleavage of lamin A. Taken together, these observations indicate that caspase-6 
activity is essential for lamin A cleavage and that when lamin A is present it 
must be cleaved in order for the chromosomal DNA to undergo complete 
condensation during apoptotic execution.