Separate metabolic pathways leading to DNA fragmentation and apoptotic chromatin condensation

Dexter Y. Sun*, Shibo Jiang, Li Mou Zheng, David M. Ojcius, John Ding E. Young

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

94 Scopus citations


Apoptosis is the predominant form of cell death observed in a variety of physiological and pathological conditions such as cancer involution, insect metamorphosis, the development of the immune and nervous systems, and embryogenesis. The typical nuclear changes taking place in apoptotic cells include extensive condensation of chromatin and internucleosomal DNA fragmentation into units of 200 base pairs. However, the mechanisms responsible for both chromatin condensation and DNA fragmentation have yet to be elucidated. In this study, micrococcal nuclease and the divalent cations, Ca2+ and Mg2+, were applied to isolated nuclei in an attempt to reconstitute in vitro the digestion of genomic DNA associated with apoptosis. Micrococcal nuclease was found to induce a typical pattern of DNA fragmentation, but did not give rise to chromatin condensation, whereas Ca2+/Mg2+ induced both chromatin condensation and DNA fragmentation in isolated mouse liver nuclei. When the endonuclease inhibitor ZnCl2 was used, the DNA fragmentation induced by Ca2+/Mg2+ in nuclei could be completely inhibited, but chromatin condensation still occurred. For comparison, intact liver cells were treated with valinomycin, a potassium ionophore, which gave rise to an atypical cell death, with chromatin condensation appearing without DNA fragmentation. Our results suggest that endonuclease activation in apoptosis is neither necessary nor sufficient to induce chromatin condensation, and that DNA fragmentation and chromatin condensation may be triggered through separate pathways during apoptosis.

Original languageEnglish
Pages (from-to)559-568
Number of pages10
JournalJournal of Experimental Medicine
Issue number2
StatePublished - 01 02 1994
Externally publishedYes


  • Animals
  • Calcium Chloride
  • Cell Death
  • Cell Nucleus
  • Chlorides
  • Chromatin
  • DNA
  • Magnesium Chloride
  • Mice
  • Micrococcal Nuclease
  • Tumor Cells, Cultured
  • Valinomycin
  • Zinc Compounds


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