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Biochemists report discovery of structure of major piece of telomerase; implications for cancer

UCLA biochemists have determined the three-dimensional structure of a major domain of telomerase, the enzyme that helps maintain telomeres ?small pieces of DNA on the ends of chromosomes that act as protective caps -- allowing DNA ends to be copied completely when cells are replicated.

This is the first major piece of telomerase for which the structure is known. Telomerase plays a key role in most cancers, and this work ultimately may lead to targets for drug intervention, the scientists said. The discovery is the cover story in the March 4 issue of the journal Molecular Cell.

"Knowledge of the structure should provide insights into how telomerase works," said Juli Feigon, professor of chemistry and biochemistry at UCLA, who led the research group. "Knowing the structure also will allow the pursuit of rational, structure-based drug design, and is a critical first step. The structure provides a potential target for drug intervention."

Feigon emphasized that her laboratory conducts basic research, and is not involved in cancer treatment.

Every time a cell divides, telomeres, which act like the plastic tips on the ends of shoelaces, get shorter. In the natural aging process, the telomeres eventually get so short that cells can no longer divide, and they die. While telomerase is turned off in most types of healthy cells in our bodies, it is active in the vast majority of cancer cells, Feigon said.

Because cancer cells divide rapidly, their telomeres should get shorter more quickly than normal cells. However, because cancer cells have high levels of telomerase activity, which rebuilds the telomeres, cancer cells can maintain the length of their telomeres indefinitely. Although it is not known whether telomerase activation is just a marker for cancer cells or involved in causing it, telomerase is an attractive target for development of anti-cancer drugs by pharmaceutical companies.

The research, which was federally funded by
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Source:University of California - Los Angeles


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