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Scientists clarify much-sought enzyme, pave road to cancer therapy

Scientists worldwide have eagerly eyed the enzyme telomerase as an ideal target for anti-cancer therapy. Active in cancer cells, which need it to divide, telomerase has sparked keen research. Biotech companies have pumped millions into finding a telomerase inhibitor.

Now a team of researchers at Johns Hopkins has taken a key step toward such anti-telomerase cancer therapy. In a report in the March issue of Cell, they describe the fundamental shape of the telomerase molecule in mammals and other vertebrates. Knowing this structure, they say, helps them pinpoint the enzyme's vulnerable spots. "This puts us far closer to finding a way to inhibit it," says molecular biologist Carol Greider, Ph.D., who led the team.

After cloning the gene for the "business end" of the telomerase molecule in 32 different animals -- from shrew to elephant -- the researchers compared the structure of the resulting enzyme. They found four common areas highly involved with the enzyme's working, regardless of animal type.

"By taking this comparative or phylogenetic approach, we learned what shape nature thought best for telomerase to work," says Greider. That shape is basically the same from animal to animal, even though parts of the enzyme differ in length and chemical makeup. It emphasizes how important the particular structure must be for telomerase to function.

Telomerase's role in cells is to maintain highly specialized bits of DNA at the ends of chromosomes. These areas, called telomeres, act as caps, protecting chromosome ends either from being degraded or from abnormally sticking to other chromosomes. Without telomeres, one scientist wrote in an earlier Cell article, the resulting chromosome instability would "wreak havoc on the genome."

Scientists have found that normal and cancer cells differ greatly with respect to telomerase. Normal cells shut down production of telomerase early on, in embryo development. In cancer cells, however, the enzyme c
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Contact: Marjorie Centofanti
mcentofanti@jhmi.edu
410-955-8725
Johns Hopkins Medical Institutions
14-Mar-2000


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