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This article is part of the supplement: 3rd World Congress of the Global Arthritis Research Network (GARN): International Arthritis Summit

Oral presentation

DNA degradation during apoptotic cell death

S Nagata

  • Correspondence: S Nagata

Author Affiliations

Department of Genetics, Osaka University Medical School, Osaka, Japan

Arthritis Res Ther 2003, 5(Suppl 3):1  doi:10.1186/ar800


The electronic version of this article is the complete one and can be found online at:


Published:12 September 2003

©

Oral presentation

Apoptosis is a principal mechanism in metazoans by which superfluous or potentially harmful cells are eliminated. Deregulation of this process leads to a variety of diseases such as cancer and autoimmune diseases. Stimuli that can induce apoptosis are relatively diverse, and include the death factors (Fas ligand, tumor necrosis factor and TRAIL), DNA damage, and oxidative stress. Regardless of the origin of the apoptotic stimulus, commitment to apoptosis leads to activation of caspases, a family of cysteine proteases. Cleavage of a select group of cellular substrates by caspases is responsible for the morphological and biochemical changes that characterize apoptotic cell death. The degradation of nuclear DNA into nucleosomal units is one of the features of apoptotic cell death, and is mediated by a caspase-activated DNase (CAD). Cells deficient in CAD undergo cell death without the DNA fragmentation, but CAD-null mice did not show any adverse phenotypes. A close examination of the apoptotic cells in these mice indicated that apoptotic cells are always in macrophages. It seems that at an early stage of apoptosis, the dying cells present an 'eat me signal' on their surface. This signal is recognized by macrophages for engulfment, and DNase II in the lysosomes of macrophages degrades DNA of apoptotic cells. Mice deficient in both CAD and DNase II genes were established, and the development of various organs was found to be severely impaired in these mutant mice. The mice accumulated a large amount of undigested DNA in macrophages in various tissues during development. This accumulation of DNA in macrophages activated the innate immunity to induce the expression of the interferon β gene. The interferon thus produced seems to be responsible for the impaired tissue development. These results indicate that the degradation of DNA during apoptotic cell death is an essential step of apoptosis to maintain mammalian homeostasis.