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For years, scientists have known that an enzyme called telomerase effectively fuels the spread of most cancers. The big problem was that no one could figure out its exact shape, a fact that has hindered attempts to target it with drugs. This summer, nearly 25 years after the molecule was discovered, scientists at the Wistar Institute solved a crucial part of its structure.

A team led by Emmanuel Skordalakes was able to produce massive quantities of telomerase by using a gene from the red flour beetle, a tiny insect that is a scourge in Southern kitchens. 

The enzyme’s role is to build telomeres, short DNA sequences that act as protective caps at the ends of chromosomes, preventing the loss of genetic information during cell division. In normal adult cells, telomerase is dormant, limiting the number of times a cell can divide and replicate. In many cancers, however, telomerase is activated, enabling unchecked cell division that produces tumors. 

Using X-ray crystallography in what has been described as a “technical tour de force,” Skordalakes revealed that telomerase has a doughnut-shaped structure and a unique protein fold never seen before. That insight could pave the way for new or modified drugs designed to halt tumor growth. 
“Telomerase is an ideal target for chemotherapy because it is active in almost all human tumors, but inactive in most normal cells,” Skordalakes said. “That means a drug that deactivates telomerase would likely work against all cancers, with few side effects.”


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