By Sean Henahan, Access Excellence 

Telomeres are DNA sequences found at the ends of eukaryotic chromosomes which maintain the fidelity of genetic information during replication. Under normal circumstances the telomeres become shorter and shorter with each cycle of cell division. A sufficiently short telomere is believed to signal the cells to stop dividing. The telomerase enzyme is a ribonucleic protein that synthesizes telomeric DNA on chromosome ends. 

About three years ago, researchers announced that telomerase appeared to be responsible for the unchecked growth of human cancer cells. Unlike normal cells, in cancer cells telomerase appears to grant the cell immortality by maintaining telomere length so that the cell never receives a signal to stop dividing. Now researchers at Colorado University in Boulder have identified the gene responsible for activating telomerase, 'telomerase reverse transcriptase'. 

"Correlation of telomerase activity and cancer has been shown previously, but there has been little evidence for a causal relationship between the two. Having the human telomerase gene may aid in testing the relationship," said Toru Nakamura, a CU-Boulder researcher, Howard Hughes Medical Institute scientist and lead author on the study. Nakamura. 

Before the discovery of the telomerase gene, "Cancer researchers knew telomerase only indirectly, by following the reaction it catalyzed," said team leader Thomas Cech, who shared the 1989 Nobel prize for chemistry. "Now we have the ability to make lots of pure telomerase to understand its properties and learn how to inhibit it." 

Telomerase contains both RNA and protein components. The RNA portion of the enzyme binds to the DNA in the telomere while the protein component lures DNA subunits into the region and attaches them to the end of the chromosome. The newly discovered protein forms a complex with the telomerase RNA and does the job of telomeric DNA synthesis, explained Nakamura. 

Researchers at the Whitehead Institute for Biomedical Research have been pursuing a similar line of inquiry to the Boulder team and announced related finding. The team announced its findings (isolation and cloning of the catalytic ic subunit of human  telomerase) simultaneously with the Boulder team. 

"The telomerase enzyme is an ideal target for chemotherapy because this enzyme is active in about 90 percent of  human tumors, but inactive in most normal cells. Pharmaceutical companies have screened  thousands of compounds to find agents capable of blocking telomerase. Now that we know the identity of the catalytic subunit, drug development should move much faster," said Dr. Robert A. Weinberg of the Whitehead Institute. 

Researchers believe the telomerase research holds particular promise for the development of new cancer diagnostic tools. The hope is that by developing ways to detect telomerase activity in cells, it may be possible to diagnose cancer early, before tumors form. 



Telomerase belongs to a class of enzymes known as reverse transcriptases that use RNA as a template for creating DNA. A number of anti-AIDS drugs were designed to inhibit reverse transcriptase in HIV, a retrovirus. The experience gained in developing anti-retroviral drugs may give cancer drug developers a head start, since reverse transcriptases share a common amino acid sequence and are expected to have similar three-dimensional structures. It is possible that variants of existing AIDS drugs might be able to inhibit telomerase. 

"The beauty of this finding is that we already know a great deal about the structure of reverse transcriptase inhibitors. We have a good starting point for developing anti-telomerase drugs," said Christopher Counter, a post-doctoral fellow in the Weinberg lab. 

The discovery of the gene for the protein called  is reported in the Aug. 15, 1997 issue of Science. The Whitehead Institute research will appear in the Aug. 21 issue of Cell (embargo permission granted by Cell).