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Allergic to your DNA?

Scientists have discovered that the presence of undigested DNA left over from dead cells can elicit an immune response in the fruit fly Drosophila, prompting researchers to question whether an analogous autoimmune response could be triggered in humans.

The report is published in the October 15th issue of Genes & Development.

Apoptosis, or programmed cell death, is a critical biological process in which superfluous or potentially harmful cells undergo a series of genetic changes that ultimately result in the death of the cell, and its engulfment by a neighboring cell. Apoptosis is involved in a number of developmental and pathological processes, including embryonic digit sculpting and cancer prevention. The morphological changes that characterize apoptosis include nuclear DNA fragmentation and digestion although research has shown that cells can undergo apoptosis without DNA degradation.

Dr. Shigekazu Nagata and colleagues at Osaka University in Japan set out to determine the biological significance of apoptotic DNA degradation.

Dr. Nagata's group used Drosophila as a model organism because apoptosis has been largely conserved throughout evolution from flies to mammals. Both fly and mammalian cells contain several DNase enzymes that specifically degrade DNA. During apoptosis, a DNase called CAD is released from its inhibitor, ICAD, and thereby activated to chop up DNA inside the dying cell. The engulfing cell also houses DNases, including DNase II enzymes inside the lysosome (a specialized cellular compartment where ingested material is digested) that are thought to play a role in apoptotic DNA degradation.

Dr. Nagata and colleagues generated strains of flies deficient in ICAD, DNase II, or both ICAD and DNase II in order to determine the relative contributions of each of these enzymes to apoptotic DNA degradation, and the physiological consequences of this process. The researchers found that ICAD-deficient flies also do n
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Contact: Heather Cosel
coselpie@cshl.org
Cold Spring Harbor Laboratory
14-Oct-2002


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