文章：

端粒功能障碍与肿瘤抑制：衰老的联系

Telomere dysfunction and tumour suppression: the senescence connection

原文发布日期：2008-06-01

DOI: 10.1038/nrc2393

类型: Review Article

开放获取: 否

要点：

1. Telomeres are TTAGGG repetitive sequences that cap the ends of eukaryotic chromosomes.
2. A core of telomere binding proteins, termed the shelterin complex, serve to protect telomeric ends.
3. Critical telomere shortening or uncapping of telomere binding proteins results in telomere dysfunction.
4. Dysfunctional telomeres activate a DNA damage response. In the setting of a competent p53 pathway, this initiates senescence and apoptotic programmes to inhibit tumorigenesis.
5. In cells with mutant p53, dysfunctional telomeres promote genome instability and progression to cancer.
6. Cellular senescence is as potent as apoptosis in suppressing spontaneous tumorigenesis in mouse models of telomere dysfunction.

要点翻译：

1. 端粒是覆盖在真核生物染色体末端的TTAGGG重复序列。
2. 一组核心的端粒结合蛋白，称为遮蔽蛋白复合体，起到保护端粒末端的作用。
3. 端粒的严重缩短或端粒结合蛋白的脱帽会导致端粒功能障碍。
4. 功能失调的端粒会激活DNA损伤反应。在p53通路健全的情况下，这会启动衰老和凋亡程序以抑制肿瘤发生。
5. 在p53突变的细胞中，功能失调的端粒会促进基因组不稳定性并进展为癌症。
6. 在端粒功能障碍的小鼠模型中，细胞衰老在抑制自发性肿瘤发生方面与细胞凋亡同样有效。

英文摘要：

Long-lived organisms such as humans have evolved several intrinsic tumour suppressor mechanisms to combat the slew of oncogenic somatic mutations that constantly arise in proliferating stem-cell compartments. One of these anticancer barriers is the telomere, a specialized nucleoprotein complex that caps the ends of eukaryotic chromosome. Impaired telomere function activates the canonical DNA damage response pathway that engages p53 to initiate apoptosis or replicative senescence. Here, we discuss how p53-dependent senescence induced by dysfunctional telomeres may be as potent as apoptosis in suppressing tumorigenesis in vivo.

摘要翻译： 

长寿命生物（如人类）已进化出多种内在抑瘤机制，以应对不断增殖的干细胞区室中持续出现的致癌体细胞突变。其中一道抗癌屏障是端粒——一种覆盖真核染色体末端的特化核蛋白复合体。端粒功能受损会激活经典DNA损伤应答通路，招募p53启动凋亡或复制性衰老。在此，我们探讨体内由端粒功能障碍诱导的p53依赖性衰老如何在抑制肿瘤发生方面可能与凋亡同样有效。

原文链接：

Telomere dysfunction and tumour suppression: the senescence connection