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March 10, 2005

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

Topics: Medicine

Telomeres are unique DNA-protein structures that contain noncoding TTAGGG repeats and telomere-associated proteins. These specialized structures are essential for maintaining genomic integrity. Alterations that lead to the disruption of telomere maintenance result in chromosome end-to-end fusions and/or ends being recognized as double-strand breaks. A large body of evidence suggests that the cell responds to dysfunctional telomeres by undergoing senescence, apoptosis, or genomic instability. In conjunction with other predisposing mechanisms, the genomic instability encountered in preimmortal cells due to dysfunctional or uncapped telomeres might lead to cancer.

But now we may be taking new steps toward new targets for cancer drugs that are yet to be developed. According to Medical News Today, 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.

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.

Selected reading for an example of drug-induced suppression of telelomerase activity with potential  therapeutic applications:

Genistein induces cell growth inhibition in prostate cancer through the suppression of telomerase activity.

Posted by Hyscience at March 10, 2005 4:32 PM



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