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Telomerase's New Talent
17 August 2005 (All day)
Telomerase is a miracle worker of sorts. Normally, when cells multiply, their chromosomes suffer wear-and-tear, and eventually their progeny can't reproduce any more. Telomerase helps cells avoid this fate by protecting chromosomes. But that's not all this enzyme does, according to a new study in mice. It can also encourage stem cells to proliferate, a finding that may suggest new strategies for tackling cancer and problems related to aging.
Telomeres are protective DNA structures at the ends of chromosomes that have been likened to the tips of shoelaces. They are refurbished in young, active cells--and in most cancers--by telomerase. In recent years, research has suggested that telomerase alone could spur cell growth without altering telomeres, which would mean it has other duties besides synthesizing new DNA tips.
Now a group at Stanford University School of Medicine, led by cancer biologist Steven Artandi, has conclusively shown this with genetically manipulated mice. The team fiddled with the two major components of telomerase: a protein called TERT and an RNA element called TERC. The researchers engineered the mice to have an extra TERT gene that could be turned on and off. They then looked at TERT's effect on hair growth. Hair, says Artandi, is a good subject to study because follicles contain tightly regulated stem cells that control hair growth.
Indeed, the researchers got an even more impressive result than they expected. Two weeks after having their backs shaved, mice who had their extra TERT gene activated showed significant hair growth. By comparison, little growth was seen either in ordinary mice or in a group of engineered mice who didn't have their extra TERT turned on. The effect on stem cell proliferation was independent of telomeres; this was demonstrated when transgenic mice lacking TERC--necessary for refurbishing telomeres--also grew hair. "This is new and important evidence that TERT may have additional roles in both normal and cancer cells," says Artandi, whose team reports its findings 18 August in Nature.
The research may help scientists understand why TERT is overexpressed in many cancers, says skin stem cell researcher Elaine Fuchs of Rockefeller University in New York City. Sheila Stewart, a cell biologist at Washington University in St. Louis, Missouri, adds that with this new insight into the workings of telomerase, scientists may need to rethink proposed ideas for using the enzyme in cancer therapy.
Unfortunately, a cure for baldness is probably not in the cards. Artandi says baldness dramatically alters hair follicles and makes it unlikely they would respond to the protein.