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UCSF study reveals mechanism of telomerase enzyme that could lead to target for cancer therapy, cell regeneration

UC San Francisco researchers have discovered a region in the telomerase enzymethat they say could prove to be a target for killing cancer cells and regenerating damaged cells, and could also lead to a possible target forattacking HIV.

The enzyme -- brought to popular fame two years ago by studies showing that it could be manipulated in cell culture to increase the life span of cells - has the capacity to replenish the tips of chromosomes, known as telomeres, which lose their final fragments with each cycle of cell division. When activated, telomerase replenishes telomeres by copying the RNA folded within it into telomeric DNA and assembling it on the ends of the chromosomes.

Telomeres maintain the stability of chromosomes in numerous ways and, much like chemical bookends, prevent them from unwinding. But in a fine illustration of nature's ingenuity, they also play a role in regulating the life span of a cell, because the tips of telomeres drop off chromosomes with each cycle of cell division.1 As the telomeres gradually shorten, the probability that they will signal the cell to stop dividing gradually increases. As a result, after many cycles of cell division have occurred, all cells in a population have died.

While the telomerase enzyme has the ability to replenish the telomeres on the ends of chromosomes, it is inactive in many adult human tissues. However, it is active when massive amounts of cell division are underway - as in self-renewing adult cells of the immune system, during the development of an embryo, and in cancer.

In the UCSF study, reported in the May 5 issue of Science, the researchers determined that a small structure within the RNA molecule of yeast telomerase controls the precision with which the enzyme carries out its key function -- spinning out the repeated sequences of telomeric DNA that bind the ends of chromosomes.

When they disrupted this small region of RNA, the enzyme began to spin out tel
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Contact: Jennifer O'Brien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
4-May-2000


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