Lack of cell cycle regulation of telomerase activity in human cells

Lack of cell cycle regulation of telomerase activity in human cells
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DOI:
10.1073/pnas.94.20.10687
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发表时间:
1997-09-30
影响因子:
11.1
通讯作者:
Wright, WE
Wright, WE
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Holt, SE;Aisner, DL;Wright, WE

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关于端粒酶活性的细胞周期调控及其在静止和细胞分化过程中可能受到的抑制,出现了相互矛盾的报道。我们重新审查了这些问题,试图找出产生差异的原因。在细胞周期中提取的端粒酶活性的变化在DNA含量的基础上分类的细胞中没有观察到。在使用一些生化细胞周期抑制剂同步的细胞中观察到变异,但仅在那些细胞毒性明显的药物中,端粒酶活性逐渐下降,其生长速度从每周7到8倍减少到每周1到2倍。在真正退出细胞周期并在7天内不分裂的细胞中,端粒酶在很大程度上是不存在的。尽管并非所有细胞类型都需要以相同的方式调节端粒酶,但我们得出结论,在检测的永生培养细胞系中,提取的端粒酶活性在细胞周期的各个阶段的进展过程中没有显著变化。端粒酶活性通常与生长速率相关,在细胞退出细胞周期并进入静止状态时受到抑制。
Conflicting reports have appeared concerning the cell cycle regulation of telomerase activity and its possible repression during quiescence and cell differentiation. We have reexamined these issues in an attempt to uncover the basis for the discrepancies. Variations in extracted telomerase activity during the cell cycle are not observed in cells sorted on the basis of DNA content. Variations are observed in cells synchronized using some biochemical cell cycle inhibitors, but only with those agents where cellular toxicity is evident, A progressive decline in telomerase activity is observed in cells whose growth rate is reduced from seven to eight population doublings per week to one to two doublings per week. Telomerase is largely absent in cells that truly exit the cell cycle and do not divide over the 7-day period, Although it is not necessary for all cell types to regulate telomerase in the same way, we conclude that in the immortal cultured cell lines examined, extracted telomerase activity does not change significantly during progression through the stages of the cell cycle. Telomerase activity generally correlates with growth rate and is repressed in cells that exit the cell cycle and become quiescent.