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Endonuclease G is an apoptotic DNase when released from mitochondria
Naturevolume 412, pages95–99 (2001)Cite this article
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Abstract
Nucleosomal fragmentation of DNA is a hallmark of apoptosis (programmed cell death)1, and results from the activation of nucleases in cells undergoing apoptosis. One such nuclease, DNA fragmentation factor (DFF, a caspase-activated deoxyribonuclease (CAD) and its inhibitor (ICAD)), is capable of inducing DNA fragmentation and chromatin condensation after cleavage by caspase-3 (refs2,3,4). However, although transgenic mice lacking DFF45 or its caspase cleavage site have significantly reduced DNA fragmentation5,6, these mice still show residual DNA fragmentation and are phenotypically normal5,6,7. Here we report the identification and characterization of another nuclease that is specifically activated by apoptotic stimuli and is able to induce nucleosomal fragmentation of DNA in fibroblast cells from embryonic mice lacking DFF. This nuclease is endonuclease G (endoG), a mitochondrion-specific nuclease that translocates to the nucleus during apoptosis. Once released from mitochondria, endoG cleaves chromatin DNA into nucleosomal fragments independently of caspases. Therefore, endoG represents a caspase-independent apoptotic pathway initiated from the mitochondria.
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Acknowledgements
We thank J. M. Peters, M. Lutter and M. Fang for their assistance in mitochondrion purification and other techniques; Y. Li and R. Harold for technical support; J. Zhang and M. Xu for providing DFF45-knockout MEF cells. We also thank M. Lutter and X. Jiang for recombinant Bcl-xL. X.L. is supported by the Leukemia Society of America; X.W. is supported by grants from NIH and the Welch Foundation.
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Howard Hughes Medical Institute & Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, Dallas, 75390, Texas, USA
Lily Y. Li, Xu Luo & Xiaodong Wang
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Correspondence toXiaodong Wang.
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Li, L., Luo, X. & Wang, X. Endonuclease G is an apoptotic DNase when released from mitochondria.Nature412, 95–99 (2001). https://doi.org/10.1038/35083620
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