Editors' ChoiceApoptosis

A Role for EndoG in Apoptosis

Science's STKE  10 Jul 2001:
Vol. 2001, Issue 90, pp. tw1
DOI: 10.1126/stke.2001.90.tw1

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]