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| |  Studies Looking at Surprising Role of Telomeres for Stopping Aging and Cancer SAN FRANCISCO--March 6, 1997 -- Bits of protective DNA on the ends of a cell's gene-harboring chromosomes -- already believed by some scientists in the biotechnology industry to hold a key to stopping aging and cancer -- now also have been shown by a pioneering academic researcher to play an entirely different and vital role in the life of a cell. New findings published in the March 7 issue of Science by Elizabeth H. Blackburn, Ph.D., and her University of California San Francisco research team reveal that "telomeres," which are end caps on chromosomes, the thin, elongated, gene-harboring structures inside cells, play an important function in controlling the separation of paired chromosomes when cells grow and divide. The fidelity of chromosome allocation during cell division is crucial in ensuring that the two daughter cells will receive neither too few nor too many genes. A normal gene complement is needed to direct the orderly production of the proteins that will guide the cell in the performance of both specialized functions and in carrying out the everyday, household tasks of any cell. In humans, abnormal chromosome allotments in fertilized eggs result in genetic disorders. For example, an extra copy of chromosome 21 causes Down’s syndrome. "While it had been known that chromosomes lacking telomeres fuse together, or degrade, or are lost at high rates, not much had been known about how telomeres ensure the stability of chromosomes," according to Blackburn, professor and chair of microbiology and immunology at UCSF. The UCSF researchers made films of cells dividing, a process called mitosis. With the aid of fluorescent tags and special light microscopic techniques developed by John W. Sedat, Ph.D., professor of biochemistry and biophysics, they demonstrated that telomeres must spell out the proper DNA sequence, specific to its own species, in order for chromosome pairs to separate normally during cell division. Mutated telomeres with strange DNA sequences stick together even as the chromosomes are being pulled apart and the cell continues its efforts to complete cell division. This tension leads to extraordinary stretching of chromosomes, sometimes to twice their normal length, and to a greatly elongated cell. Blackburn and others previously demonstrated that telomeres prevent genes from being lost when cells replicate their chromosomes. Cells perform their chromosome-duplicating duties prior to allocating the resultant genetic material to two new daughter cells and completing the process of cell division. However, when a cell's chromosomes are replicated, the DNA-replicating machinery normally fails to copy the DNA at the chromosomes' tips. Telomeres make up for this oversight by serving as sacrificial DNA. In the same way that the caps on sneaker laces prevent fraying, the telomeres, which are made of DNA but contain no genes, surrender a bit of themselves and thereby help prevent chromosomes from being damaged and genes from being lost when cells divide. Blackburn works primarily with single-celled organisms, including yeast and, for the research reported in Science, a pond-dweller called Tetrahymena. In 1985, Blackburn and her graduate student Carol E. Greider, working with Tetrahymena, reported the discovery of telomerase, an enzyme responsible for assembling and adding telomeric DNA to the ends of chromosomes. Blackburn speculates that as-yet-unidentified proteins may oversee the function of telomeres in chromosome separation and points out that several proteins have recently been identified that play The idea that aging and cancer might be stopped by manipulating the mortality of normal and malignant cells through telomeres has generated excitement in the biotechnology industry. To achieve these aims, researchers are looking into controlling the integrity of telomeres by controlling activity of the telomerase enzyme. Studies of human cells from several different tissues have provided evidence that the cells' telomeres are shorter in older individuals and that telomerase is inactive in these cells. Company scientists reason that preserving the telomere caps may enable cells to healthily survive additional cell divisions, rejuvenating the aging organism of which they are part. Conversely, they say, doing away with telomeres by eliminating telomerase activity in tumors may lead to massive genetic damage, inducing seemingly immortal cancer cells to cease their relentless replications and die. Whatever the merits of the idea of controlling the mortality of our cells and of ourselves by controlling telomeres, the generalization that telomere length shortens over time in the progeny of normal cells while being maintained by telomerase activity in cancer cells is now being challenged by a messier picture of telomeric reality emerging from additional studies in several labs, Blackburn says.
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