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Caspase-6 gene disruption reveals a requirement for lamin A cleavage in apoptotic chromatin condensation

Lookup NU author(s): Professor Colin Dingwall

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Abstract

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 wildtype 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.

Publication metadata

Author(s): Dingwall C; Ruchaud S; Korfali N; Villa P; Kottke TJ; Kaufmann SH; Earnshaw WC

Publication type: Article

Publication status: Published

Journal: EMBO Journal

Year: 2002

Volume: 21

Issue: 8

Pages: 1967-1977

ISSN (print): 0261-4189

ISSN (electronic): 1460-2075

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1093/emboj/21.8.1967

DOI: 10.1093/emboj/21.8.1967

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