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

Sandrine Ruchaud, Nadia Korfali, Pascal Villa, Timothy J. Kottke, Colin Dingwall, Scott H. Kaufmann, William C. Earnshaw

Research output: Contribution to journalArticle

198 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)1967-1977
Number of pages11
JournalEMBO Journal
Volume21
Issue number8
DOIs
StatePublished - Apr 15 2002

Keywords

  • Apoptosis
  • Caspase-6
  • Chromatin condensation
  • DT40
  • Lamins

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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