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University of Cincinnati Academic Health Center
Publish Date: 02/11/04
Media Contact: AHC Public Relations, (513) 558-4553
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UC Research Reveals Key Cellular Function

The same enzyme that ensures cells undergo normal, programmed death is also necessary for proper formation of the embryo, according to an article that appeared in a December issue of the Proceedings of the National Academy of Sciences (PNAS). 

Without programmed death, or apoptosis, cells would continue to proliferate indefinitely, leading to cancerous tumors.  During programmed or normal cell death, a series of events leads to the eventual consumption of the cell by roving sentinels.  One important step is the release of an enzyme called endonuclease G from the mitochondria inside the cell and its transport to the nucleus of the cell where it cleaves apart the DNA and the cell dies.

Jianhua Zhang, PhD, and Ming Xu, PhD, both faculty members at the UC Department of Cell Biology, Neurobiology and Anatomy, and colleagues investigated the role of this enzyme by developing strains of mice that were unable to produce the enzyme endonuclease G.  Mice missing one copy of the gene had cells that were resistant to normal cell death or apoptosis. 

Although this enzyme has been implicated in the replication of mitochondrial DNA, the numbers of mitochondrial DNA were the same in mutant and wild-type mice.  Interestingly, the researchers were unable to produce mice missing both copies of the endonuclease G gene. Dr. Zhang and Dr. Xu said endonuclease G may play an essential role in remodeling the structure of the developing embryo through apoptosis, from a solid ball of cells to a hollow one that is not viable.

Dr. Zhang and Dr. Xu's research study demonstrates how this enzyme confers life and death.  Results of their study were reported in the PNAS article #03-6393 and titled "Endonuclease G is required for early embryogenesis and normal apoptosis in mice."

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