No End in Sight for the Telomere Story

Release Date:
Doris Brody, NIGMS

Telomeres, the structures at the tips of chromosomes, are involved in a number of basic cellular processes and have intriguing associations with cellular aging and cancer. In normal human cells, telomeres become progressively shorter with age, but the telomeres of most cancer cells become abnormally elongated. This may be because an enzyme called telomerase, which keeps telomeres from getting shorter by adding DNA back to the chromosome ends and which is active in normal human cells for only a short time after birth, somehow becomes reactivated in cancer cells.

Because of telomeres' significant connection to human health, it is not surprising that basic researchers have been enthusiastically studying these structures nor that, for the third year in a row, several important research advances have occurred in this area.

One advance was made by Nobel Laureate and NIGMS grantee Dr. Thomas Cech and his group at the University of Colorado at Boulder, which found the gene that codes for the protein that makes up the active subunit of human telomerase. This gene shows close similarities to the telomerases of other species, implying that findings in lower organisms should be applicable to humans. The researchers determined that mutations in the gene result in shortened telomeres and cellular aging in yeast. This could lead to the identification of compounds that inhibit the activity of telomerase, which would permit researchers to discover if such inhibition will kill tumors. In addition, the scientists found a correlation between the expression of the subunit gene and human telomerase activity--a finding that might lead to relatively simple diagnostic tests for cancer.

Also this year, a critical function of telomeres in cell division was discovered by another NIGMS grantee, Dr. Elizabeth Blackburn, the researcher who first discovered telomerase a decade ago, and her group at the University of California, San Francisco. They have found that telomeres play a role in the chromosome separation that occurs before cells divide. In these studies, the chromosomes of cells that had mutant telomerase failed to separate and eventually died. The researchers believe that these results indicate that a physical block occurred during separation, and research is under way to learn the molecular details of this surprising finding.

Another NIGMS-supported researcher who is in the forefront of telomere research, Dr. Titia de Lange, and her group at The Rockefeller University, have found a protein, called TRF1, that suppresses telomere elongation in tumor cells. This protein does not inhibit the expression of telomerase, so the researchers believe it probably controls length by inhibiting the action of telomerase at the ends of the telomeres themselves. Dr. de Lange proposes that TRF1 is involved in a negative feedback mechanism that stabilizes telomere length in cancer cells. Her group is actively investigating this new level of complexity in the telomere story.

Each of these findings is important in itself. Together, they represent a significant advance in the field of telomere research.


Nakamura T, Morin G, Chapman K, Weinrich S, Andrews W, Lingner J, Harley C, Cech T. Telomerase catalytic subunit homologs from fission yeast and human. Science 1997;277:955-9.

Kirk K, Harmon B, Reichardt I, Sedat J, Blackburn E. Block in anaphase chromosome separation caused by a telomerase template mutation. Science 1997;275:1478-81.

van Steensel B, de Lange T. Control of telomere length by the human telomeric protein TRF1. Nature 1997;385:740-3.

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