Stewart Sheila A
Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
Mol Interv. 2002 Dec;2(8):481-3. doi: 10.1124/mi.2.8.481.
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.
正常情况下，细胞分裂会导致端粒缩短，端粒是位于线性染色体末端的核蛋白复合体。当端粒达到临界短长度时，细胞停止分裂。然而，永生肿瘤细胞表现出稳定的端粒长度，并能够维持其增殖状态。王和同事们发现，在细胞周期的某些阶段，端粒酶被核仁隔离，降低了端粒酶在S期晚期之前接触染色质的可能性。此外，他们证明电离辐射倾向于使端粒酶被隔离在核仁中，而细胞转化则导致端粒酶易位到核质中，在那里它大概可以在适当和不适当的位点催化端粒延长。因此，端粒酶的隔离对端粒酶活性施加了一种新发现的调节水平，这意味着端粒酶定位可能是药物治疗的一个有用靶点。
