Is telomerase moonlighting?

The debate continues as to whether telomerase's only function is to promote telomere extension.

Graciela Flores
Sep 25, 2005
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© 2005 Nature Publishing Group

The debate continues as to whether telomerase's only function is to promote telomere extension. In recent years evidence has suggested that the enzyme promotes cancer development and might have roles other than synthesizing telomere repeats. Now, Kavita Sarin of Stanford University and colleagues report that telomerase promotes proliferation of resting stem cells through a mechanism that does not involve telomere extension.1

The team studied the murine hair follicle, an organ that harbors stem cells and cycles between a telogen (resting) phase and an anagen (growing) phase. They built transgenic mice in which they could control the expression of TERT – the protein component of telomerase – using a tetracycline regulatory system.

With TERT switched on, the overexpressed protein promotes the transition from telogen to anagen through activation and proliferation of quiescent stem cells in the follicle, creating shaggy mice. In mice that completely lacked TERC – the RNA portion of telomerase that enables the enzyme to make telomere DNA – the effects of TERT remained.

"It's the clearest demonstration of something that has been accumulating for a while," says Elizabeth H. Blackburn of the University of California, San Francisco. Jerry W. Shay, at the University of Texas Southwestern Medical Center at Dallas, agrees that the studies provide additional evidence, but is not convinced. "Overexpressing a transgene, in this case telomerase, with a strong promoter could be indirectly causing the effect."