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Cech To Discuss 'Life at the End of the Chromosome'

By Doug Dollemore

On the Front Page...

Scientists are hot on the trail of an enzyme that has the potential to increase the longevity of normal cells and may provide new tools to attack malignant ones, says Nobel laureate Dr. Thomas R. Cech. The enzyme, called telomerase, synthesizes or extends chromosome endings in germ cells, and may act like a molecular "timer" to regulate how long chromosomes in non-germ cells can continue to function.

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Cech will discuss what is known about telomerase and its possible impact on lifespan and health when he delivers the NIH Director's Lecture on Wednesday, Sept. 20 at 3 p.m. in Masur Auditorium, Bldg. 10. His lecture, "Life at the End of the Chromosome: Telomeres and Telomerase," will include a glimpse at emerging findings about this unusual enzyme.

Dr. Thomas R. Cech

To grasp the significance of telomerase, it helps to know a bit about chromosomes. Each human chromosome consists of one long DNA molecule tightly wound around a scaffold made of several proteins. Both ends of the DNA molecule are formed of hundreds of copies of the same short DNA sequence, repeated over and over. These sequences, which are part of chromosome end structures called telomeres, become progressively shorter each time the cell divides. Researchers suspect that this shortening is one of the critical features of cellular aging.

Over time, telomeres become so short that the chromosomes they are attached to can no longer duplicate. This, in turn, leads the cell to stop dividing. But cancer cells are somehow able to reactivate telomerase, allowing them to escape mortality and grow in number indefinitely.

Some researchers believe if telomerase can be artificially regulated so that its activity is either activated or blocked, it has the potential to slow aging and, perhaps, slow the growth of cancers. But like many mechanisms in the body, the role of telomerase is probably very complex, Cech says. For now, his team is studying telomerase in ciliated protozoa and yeast to focus on three questions: How does this enzyme work? How and where in the cell is the enzyme assembled? And how do telomere-telomerase interactions control the replication of chromosome ends?

"These simple organisms allow us to manipulate telomerase both in the laboratory and in living cells, yet we have reason to believe that many of our findings will hold true for human telomerase as well," Cech said.

He received the Nobel Prize in chemistry in 1989, shared with Sidney Altman of Yale University, for their independent discoveries of ribozymes, ribonucleic acid (RNA) molecules that not only convey genetic information, but also act as enzymes. He became interested in telomeres and telomerase when researchers Elizabeth Blackburn and Carol Greider determined that telomerase is composed of two subunits. One is made of RNA, which serves as a template for the DNA sequences that comprise the telomeres. The other subunit is a protein that catalyzes the chemical reaction that adds the DNA sequences to the ends of the chromosomes.

Cech earned his doctorate at the University of California, Berkeley, and was a postdoctoral fellow at the Massachusetts Institute of Technology. In 1978, he joined the faculty of the department of chemistry at the University of Colorado, Boulder. He has received continuous NIH funding for his work since 1978. He was a Howard Hughes Medical Institute investigator from 1988 to 1999. Earlier this year, he was appointed president of that institution. HHMI, a nonprofit medical research organization headquartered in Chevy Chase, employs hundreds of leading biomedical scientists working at the forefronts of biomedical research.

Cech is a member of the National Academy of Sciences and the American Academy of Arts and Sciences. He has received numerous prizes and awards, including the Pfizer Award in Enzyme Chemistry, and the National Medal of Science, which was presented to him by President Clinton at a White House ceremony in 1995. He has received honorary doctorates from Grinnell College, the University of Chicago and the University of Maryland, Baltimore.

The lecture is an NIH Wednesday Afternoon Lecture Series event, hosted by the National Institute on Aging. For more information or accommodation, phone Hilda Madine, 594-5595.


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