A Role for EndoG in Apoptosis

Abstract

During apoptosis, DNA is cleaved by enzymes, which assures that the death event is inexorable. Two proteins with known nuclease activity have been implicated in apoptosis: the Caenorhabditis elegans DNAse II-like protein termed NUC-1, and the mammalian DNAse termed CAD (caspase-activated DNAse). Now another nuclease can be added to the list: endonuclease G (EndoG). Li et al. found that isolated mitchondria treated with apoptosis-inducing Bid released EndoG. EndoG activation apparently did not require the proteolytic digestion of a bound inhibitory protein; rather, release from the mitochondria was sufficient for its activation. Additionally, in CAD-deficient cells, EndoG was able to carry out caspase-independent digestion of DNA, indicating that EndoG activity alone may be sufficient for DNA fragmentation. Parrish et al. showed that CPS-6, a C. elegans protein that bears considerable sequence similarity to EndoG, also participates in cell death in the worm. cps-6 mutant worms had decreased cell death during their development. These results were also seen in experiments using RNA interference to reduce the amount of CPS-6 expressed in worms. Hengartner writes a synopsis of the papers and discusses the implications of these articles on apoptosis research. L. Y. Li, X. Luo, X. Wang, Endonuclease G is an apoptotic DNase when released from mitochondria. Nature 412 , 90-94 (2001). [Online Journal] J. Parrish, L. Li, K. Klotz, D. Ledwich, X. Wang, D. Xue, Mitochondrial endonuclease G is important for apoptosis in C. elegans . Nature 412 , 95-99 (2001). [Online Journal] M. O. Hengartner, DNA destroyers. Nature 412 , 27-29 (2001). [Online Journal]