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Structure determined for key molecular complex involved in long-term gene storage

PHILADELPHIA Around the home, regularly used tools are generally kept close at hand: a can opener in a kitchen drawer, a broom in the hall closet. Less frequently used tools are more likely to be stored in less accessible locations, out of immediate reach, perhaps in the basement or garage. And hazardous tools might even be kept under lock and key.

Similarly, the human genome has developed a set of sophisticated mechanisms for keeping selected genes readily available for use while other genes are kept securely stored away for long periods of time, sometimes forever. Candidate genes for such long-term storage include those required only for early development and proliferation, potentially dangerous genes that could well trigger cancers and other disorders should they be reactivated later in life. Cancer researchers and others have been eager to learn more about the molecules that direct this all-important system for managing the genome.

Now, researchers at The Wistar Institute and Fox Chase Cancer Center have successfully determined the three-dimensional structure of a key two-molecule complex involved in long-term gene storage, primarily in cells that have ceased proliferating, or growing. The study also sheds light on a related two-molecule complex that incorporates one member of the molecular pair, but with a different partner. This second complex is involved in storing genes in a more accessible way in cells that continue to grow. A report on the team's findings, published online on September 17, will appear in the October issue of Nature Structural and Molecular Biology.

"The two-molecule complex we studied is pivotal for protecting certain genes from expression, genes that could cause problems if they were activated," says Ronen Marmorstein, Ph.D., a professor in the Gene Expression and Regulation Program at Wistar and one of the two senior authors on the study. "This is the first time we've been able to see the structure of thes
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Contact: Franklin Hoke
hoke@wistar.org
215-898-3716
The Wistar Institute
17-Sep-2006


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