p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2
p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2
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DOI：
10.1126/science.283.5406.1321
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发表时间：
1999-02-26
期刊：
影响因子：
56.9
通讯作者：
de Lange, T
中科院分区：
文献类型：
--
作者：
Karlseder, J;Broccoli, D;de Lange, T
虽然断裂的染色体可以诱导细胞凋亡，但天然染色体末端（端粒）不会引发这种反应。研究表明，这种细胞凋亡的抑制涉及端粒重复序列结合因子2（TRF2），TRF2的抑制导致哺乳动物细胞类型的一个子集中的细胞凋亡，这种反应是由p53和ATM（共济失调毛细血管扩张突变）激酶介导的，与DNA损伤检查点的激活一致。细胞凋亡不是由于端对端融合形成的双着丝粒染色体的断裂，这表明缺乏TRF2的端粒直接发出细胞凋亡的信号，可能是因为它们类似于受损的DNA。因此，在某些细胞中，端粒缩短可能是细胞死亡而不是衰老的信号。
Although broken chromosomes can induce apoptosis, natural chromosome ends (telomeres) do not trigger this response. It is shown that this suppression of apoptosis involves the telomeric-repeat binding factor 2 (TRF2), Inhibition of TRF2 resulted in apoptosis in a subset of mammalian cell types, The response was mediated by p53 and the ATM (ataxia telangiectasia mutated) kinase, consistent with activation of a DNA damage checkpoint. Apoptosis was not due to rupture of dicentric chromosomes formed by end-to-end fusion, indicating that telomeres Lacking TRF2 directly signal apoptosis, possibly because they resemble damaged DNA. Thus, in some cells, telomere shortening may signal cell death rather than senescence.