Endonuclease G is an apoptotic DNase when released from mitochondria.
Nucleosomal fragmentation of DNA is a hallmark of apoptosis (programmed cell death), 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 (refs 2,3,4). However, although transgenic mice lacking DFF45 or its caspase cleavage site have significantly reduced DNA fragmentation, these mice still show residual DNA fragmentation and are phenotypically normal. 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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Howard Hughes Medical Institute & Department of Biochemistry, University of Texas Southwestern Medical Center at Dallas, 75390, USA.
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D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism; D004247:DNA / Q000378:metabolism / Q000528:radiation effects; D004706:Endodeoxyribonucleases / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008930:Mitochondria, Liver / Q000201:enzymology*; D011506:Proteins / Q000378:metabolism; D011994:Recombinant Proteins; D014466:Ultraviolet Rays
D051017:Apoptosis Regulatory Proteins; D003574:Cytochrome c Group; D011506:Proteins; D011994:Recombinant Proteins; C109664:caspase-activated DNase inhibitor; D004247:DNA; D004706:Endodeoxyribonucleases; C052391:endonuclease G; C505530:CASP8 protein, human; C506433:CASP9 protein, human; C505526:Casp8 protein, mouse; C506434:Casp9 protein, mouse; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases