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UCSF scientists halt tumor growth by manipulating telomerase enzyme

the study, Elizabeth Blackburn, PhD, UCSF professor of biochemistry and biophysics. "Cancer cells are tough. They usually ignore the signals that tell them to commit suicide. But by spiking the telomerase enzyme with just a little bad telomerase we saw a powerful effect." Blackburn, in 1985, co-discovered the telomerase enzyme.

The study is published in the July 3 issue of Proceedings of the National Academy of Sciences.

The researchers created the mutation in a minute portion of the enzyme's template, a sequence of ribonucleic acid (RNA) that the enzyme synthesizes into deoxyribonucleic acid (DNA) and places on the tips of telomeres, DNA-protein complexes at the ends of chromosomes. Telomeres maintain the integrity of chromosomes and their ability to divide accurately during cell division. However, the tips of telomeres drop off each time a cell divides, and when they are gone a cell stops dividing. (This built-in limit on cell division, known as the Hayflick limit, was discovered in 1961 by UCSF adjunct professor of anatomy Leonard Hayflick, PhD.) The telomerase's ability to spin out DNA from an RNA template - a technique known as reverse transcriptase - to replenish telomeres is essential to the life of dividing cells.

The mutation within the telomerase RNA - which itself is a mere 450 nucleotides - was a tenth the size of a typical gene. Notably, it did not alter most telomeres' lengths. The finding suggests, says Blackburn, that "uncapping" of only one or a few telomeres per cell by the mutant telomerase can trigger a DNA damage response, thereby inducing cell-cycle arrest or inducing cell death in human cancer cells.

The researchers plan to explore the strategy in human cancer cells freshly derived from patients - as opposed to those in the current study, which were grown continuously in the lab dish. (Researchers suspect that cancer cells grown in culture adapt for growth - changing their genetic content - and thus may behave
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Contact: Jennifer O'Brien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
2-Jul-2001


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