Telomerase enzyme structure provides significant new target for anti-cancer...( (PHILADELPHIA) Inappropriate activa...),Health

(PHILADELPHIA) Inappropriate activation of a single enzyme, telomerase, is associated with the uncontrollable proliferation of cells seen in as many as 90 percent of all of human cancers. Since the mid-1990s, when telomerase was first identified in human tumors, scientists have eyed the enzyme as an ideal target for developing broadly effective anti-cancer drugs.

Now, researchers working at The Wistar Institute have brought this goal closer by deciphering the three-dimensional structure of a domain, or region, of the telomerase molecule essential for the activity of the enzyme. The findings, published November 13 in the journal Structure, may help scientists develop strategies to design the first direct inhibitors of telomerase.

Telomerase also has been shown to play a central role in normal aging, and the new study may shed light on that vital life process as well. The potential for creating new cancer treatments, however, is the most important immediate implication of the study.

Knowing the physical structure of this complex will give pharmaceutical companies a direct target for designing drugs that disrupt a mechanism that telomerase uses to assemble itself, says Emmanuel Skordalakes, Ph.D., an assistant professor in the Gene Expression and Regulation Program at Wistar and senior author on the study. Such drugs could well have significant anti-cancer activity.

Telomerase is essential for normal cell division and survival, and has been associated with aging and cancer. In humans, the usual role of telomerase is to add multiple repeats of a short length of DNA to the ends of chromosomes, known as telomeres, thus preventing damage and the loss of genetic information during DNA replication. It performs this critical service in developing embryos and in a few specialized cell lines, including stem cells.

In normal adult cells, however, telomerase is switched off almost entirely to prevent the dangers of runaway cell
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