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Landmark study opens door to new cancer, aging treatments
Date:8/31/2008

"That was really the breakthrough," Skordalakes says. "Once we found that the gene from this organism expressed the protein in the quantities we needed, we were able to move quickly."

The researchers used X-ray crystallography, a technique that analyzes the diffraction patterns of X-rays beamed at crystals of a molecule, to determine the three-dimensional structure of the enzyme's active regionthe catalytic component called telomerase reverse transcriptase protein, or TERT.

The study revealed surprising features, including the fact that the molecule's three domains are organized into a doughnut shape, an unexpected configuration. Knowledge of the structure allowed the researchers to create a model of the enzyme's function.

"It's extremely exciting," Skordalakes says. "For the first time, we can see how telomerase assembles at the end of chromosomes to initiate telomere replication."

Looking ahead

Skordalakes plans to further study TERT and search for new telomerase inhibitors that could become cancer therapies. He also will look at modifying existing drugs. Previous attempts to target telomerase have fallen flat, but knowledge of the enzyme's structure will help researchers to determine the limitations of existing agents and make them more effective.

Skordalakes began his studies of telomerase when he joined The Wistar Institute in 2006 and established his first laboratory. "I've always been interested in understanding, on a molecular level, the function of protein nucleic acid assemblies and using that information in the treatment of human disease," he says. "Telomerase, because of its important role in cancer and aging, was an obvious target for me."

He says though the process was frustrating at times, his team was determined to solve the structure. "It required a lot of perseverance and effort, but we really wanted to do this," he says.


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Contact: Abbey J. Porter
aporter@wistar.org
215-898-3943
The Wistar Institute
Source:Eurekalert

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