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ESSENTIAL TELOMERE PROTEIN
By Sean Henahan, Access Excellence Boulder, CO (4/25/97) The discovery of an essential protein component of telomerase could speed development of new cancer diagnostic tests and treatments. The telomere is the section of DNA found at the tip of each chromosome in nonbacterial cells. Replication of telomeres is regulated by a special enzyme called telomerase. Telomerase is unusual because it contains RNA. The observation that telomerase was activated in many cancer cells led to considerable research in recent years. A team of researchers has now identified the catalytic protein subunit of telomerase. Amazingly, the protein, called p123, closely resembles reverse transcriptase, an enzyme essential for replication of retroviruses including HIV. Reverse transcriptase facilitates the onset and spread of HIV by copying RNA into DNA and inserting it into the chromosome of hosts. Reverse transcriptase proteins can also shuffle genetic information within the cells, he said.  The researchers showed that changing even a single amino acid out of the 884 acids in the enzyme's chain prevented telomerase from working in living yeast cells. Cells carrying a mutant telomerase protein gradually lost DNA from their chromosome ends and ceased growing after about 75 generations. "These changes obliterated telomerase activity in living cells and in the test tube, providing strong evidence the new protein provides the active center of the telomerase. It is a great irony that a protein essential for complete replication of chromosomes has the same detailed shape as the protein responsible for the replication of HIV," said Thomas Cech, professor of chemistry and biochemistry at the University of Colorado and a Howard Hughes Medical Institute Investigator. Cech shared the 1989 Nobel Prize in chemistry. Telomerase, which has been shown to be active in about 85 percent of cancer cells, is not found in adjacent, healthy cells, said the researchers. It may be possible to develop a drug that could "turn off" the production of telomerase in cancer cells, causing them to revert to normal activity, the researchers speculated. Conversely, treatments for AIDS targeting reverse transcriptase may prove to be useful anti-cancer agents. The study appears in the April 25, 1997 issue of Science. Related information on the Internet
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