Department of Biology, University of Utah, Salt Lake City, Utah, USA.
PLoS Genet. 2011 Jun;7(6):e1002103. doi: 10.1371/journal.pgen.1002103. Epub 2011 Jun 2.
The mechanisms that cells use to monitor telomere integrity, and the array of responses that may be induced, are not fully defined. To date there have been no studies in animals describing the ability of cells to survive and contribute to adult organs following telomere loss. We developed assays to monitor the ability of somatic cells to proliferate and differentiate after telomere loss. Here we show that p53 and Chk2 limit the growth and differentiation of cells that lose a telomere. Furthermore, our results show that two copies of the genes encoding p53 and Chk2 are required for the cell to mount a rapid wildtype response to a missing telomere. Finally, our results show that, while Chk2 functions by activating the p53-dependent apoptotic cascade, Chk2 also functions independently of p53 to limit survival. In spite of these mechanisms to eliminate cells that have lost a telomere, we find that such cells can make a substantial contribution to differentiated adult tissues.
细胞用于监测端粒完整性的机制，以及可能引发的一系列反应，尚未完全定义。迄今为止，尚无动物研究描述细胞在端粒丢失后存活并为成年器官做出贡献的能力。我们开发了检测端粒丢失后体细胞增殖和分化能力的方法。在这里，我们发现 p53 和 Chk2 限制了端粒丢失的细胞的生长和分化。此外，我们的结果表明，编码 p53 和 Chk2 的两个基因的拷贝对于细胞对缺失的端粒快速产生野生型反应是必需的。最后，我们的结果表明，虽然 Chk2 通过激活 p53 依赖性凋亡级联反应发挥作用，但 Chk2 也独立于 p53 发挥作用以限制存活。尽管存在消除失去端粒的细胞的这些机制，但我们发现这些细胞可以为分化的成年组织做出重大贡献。
