Leftover DNA activates innate immunity

The biochemical changes that characterize apoptosis include nuclear DNA fragmentation and digestion, but the biological importance of undigested apoptotic DNA degradation has been unclear. In October 15 Genes & Development, Naomi Mukae and colleagues at Osaka University Medical School, Osaka, Japan, show that chromosomal DNA that escapes apoptotic degradation can induce activation of the innate immunity in Drosophila (Genes & Development, 20: 2662-2671, October 15, 2002).

Mukae et al. used Drosophila lines deficient in either the gene that controls caspase-activated DNase (ICAD) inhibition or lysosomal acid DNase (dDNase II). They observed that CAD and DNase II work independently to degrade chromosomal DNA during apoptosis. The dDNase II-deficient flies showed enhanced apoptotic DNA fragmentation, yet accumulated a large amount of DNA, particularly in ovaries, and constitutively expressed the genes for antibacterial peptides. In addition, the activation of the antibacterial peptide genes was enhanced in Drosophila mutants that lacked both dICAD and ...