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Enzyme shown to help protect genomic stability

PHILADELPHIA Genomes throughout the animal kingdom and beyond are characterized by extensive segments that are inactive, lengthy stretches of DNA containing multiple genes that are closed to gene transcription. Scientists believe one reason for this broad gene silencing is the vital need for genomic stability, for protection against unwanted recombinations of genetic material or other disruptions of the genome's integrity.

Genomic instability, particularly in the regions at the ends of the chromosomes known as telomeres, has been linked to aging in humans and an elevated risk for aging-related diseases, the most prominent of which is cancer. For this reason, insights into the mechanisms of gene silencing could provide important guideposts for new approaches to retarding aging or treating cancer.

Now, an investigation led by researchers at The Wistar Institute has shown that an enzyme known as Ubp10 plays a vital role in protecting the telomeric regions of the genome from potential destabilizing molecular events. The enzyme helps to keep the genome structurally closed, unavailable for transcription and possibly protected from dangerous genetic recombinations with other regions of the genome. A report on the research, which was conducted in yeast, appears in the February 18 issue of Molecular Cell.

"There are regions of the genome that have to be inaccessible," says Shelley L. Berger, Ph.D., the Hilary Koprowski Professor in the gene expression and regulation program at Wistar and senior author on the study. "Otherwise, they can recombine with themselves or with other DNA segments. In the telomeres, such events may accelerate aging or trigger cancer in humans."

"We have identified a molecular mechanism to explain how this enzyme helps keep telomeric DNA silenced and potentially protects the genome from destabilizing activity," says N.C. Tolga Emre, a graduate student in Berger's laboratory and lead author on the study.

The Ubp
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Contact: Franklin Hoke
hoke@wistar.upenn.edu
215-514-6655
The Wistar Institute
17-Feb-2005


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