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PubMed · 10339431

Apoptotic nuclear morphological change without DNA fragmentation.

H Sakahira·M Enari·Y Ohsawa·Y Uchiyama·S Nagata
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Abstract

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] [3] [4] [5] [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.

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ApoptosisCell NucleusChromatinCysteine Proteinase InhibitorsDNA FragmentationHumansJurkat CellsMicroscopy, ElectronJournal ArticleResearch Support, Non-U.S. Gov't

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H Sakahira, M Enari, Y Ohsawa, Y Uchiyama, S Nagata. 1999-05-20. Apoptotic nuclear morphological change without DNA fragmentation.. https://doi.org/10.1016/s0960-9822(99)80240-1

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