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Multiple Levels of Telomerase Regulation

Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142

SUMMARY

Normally, cell division leads to shortening of telomeres, the nucleoprotein complexes located at the ends of linear chromosomes. When telomeres reach a critically short length, cells cease to divide. However, immortal tumor cells display stable telomere lengths and are able to maintain their proliferative state. Wong and colleagues have found that telomerase is sequestered by nucleoli during certain stages of the cell cycle, decreasing the likelihood of telomerase access to chromatin until the late S phase. Additionally, they demonstrate that ionizing radiation tends to keep telomerase sequestered in nucleoli, whereas cell transformation leads to telomerase translocation into the nucleoplasm, where, presumably, it can catalyze the lengthening of telomeres at appropriate and inappropriate sites. The sequestration of telomerase thus imposes a newly identified level of regulation on telomerase activity, implicating telomerase localization as a potentially useful target for pharmacotherapy.

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