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April 2004 Issue

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UC Research Reveals Key Celluar Function

Published April 2004

The enzyme that ensures cells undergo normal, programmed death is also necessary for proper formation of the embryo, according to an article that appeared in the December 2003 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 apoptosis, a series of events leads to the eventual consumption of the cell. 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 in the UC Department of Cell Biology, Neurobiology and Anatomy, 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. Drs. Zhang and 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.

This research study demonstrates how endonuclease G 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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