Apoptotic nuclear morphological change without DNA fragmentation

Hideki Sakahira, Masato Enari, Yoshiyuki Ohsawa, Yasuo Uchiyama, Shigekazu Nagata

    Research output: Contribution to journalArticle

    126 Scopus citations


    Apoptosis is characterized morphologically by condensation and fragmentation of nuclei and cells and biochemically by fragmentation of chromosomal DNA into nucleosomal units [1]. CAD, also known as CPAN or DFF-40, is a DNase that can be activated by caspases [2-6]. CAD is complexed with its inhibitor, ICAD, in growing, non-apoptotic cells [2,7]. Caspases that are activated by apoptotic stimuli [8] cleave ICAD. CAD, thus released from ICAD, digests chromosomal DNA into nucleosomal units [2,3]. Here, we examine whether nuclear morphological changes induced by apoptotic stimuli are caused by the degradation of chromosomal DNA. Human T-cell lymphoma Jurkat cells, as well as their transformants expressing caspase-resistant ICAD, were treated with staurosporine. The chromosomal DNA in Jurkat cells underwent fragmentation into nucleosomal units, which was preceded by large-scale chromatin fragmentation (50-200 kb). The chromosomal DNA in cells expressing caspase-resistant ICAD remained intact after treatment with staurosporine but their chromatin condensed as found in parental Jurkat cells. These results indicate that large-scale chromatin fragmentation and nucleosomal DNA fragmentation are caused by an ICAD-inhibitable DNase, most probably CAD, whereas chromatin condensation during apoptosis is controlled, at least in part, independently from the degradation of chromosomal DNA.

    Original languageEnglish (US)
    Pages (from-to)543-546
    Number of pages4
    JournalCurrent Biology
    Issue number10
    StatePublished - May 20 1999


    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)
    • Agricultural and Biological Sciences(all)

    Cite this

    Sakahira, H., Enari, M., Ohsawa, Y., Uchiyama, Y., & Nagata, S. (1999). Apoptotic nuclear morphological change without DNA fragmentation. Current Biology, 9(10), 543-546. https://doi.org/10.1016/S0960-9822(99)80240-1