Role of telomeres and telomerase in genomic instability, senescence and cancer
Role of telomeres and telomerase in genomic instability, senescence and cancer
复制标题
DOI：
10.1038/labinvest.3700673
复制
发表时间：
2007-11-01
影响因子：
5
通讯作者：
Chang, Sandy
中科院分区：
文献类型：
--
作者：
Deng, Yibin;Chang, Sandy
端粒是一种核糖核蛋白结构，它保护线性染色体的末端免受DNA双链断裂和DNA损伤反应的激活。端粒相关蛋白也调节端粒酶，这种蛋白质负责维持端粒长度。端粒功能的丧失要么是端粒封顶功能的改变，要么是维持端粒结构所需的端粒重复序列的逐渐丧失。功能失调的端粒激活p53，启动细胞衰老或凋亡，抑制肿瘤发生。然而，在缺乏p53的情况下，端粒功能障碍是人类癌症中常见的产生染色体不稳定的重要机制。端粒酶在大多数人类癌症中表达，使其成为一个有吸引力的治疗靶点。目前正在进行临床试验的抗端粒酶疗法可能对某些形式的人类癌症有用。
Telomeres are ribonucleoprotein structures that protect the end of linear chromosomes from recognition as DNA double-stranded breaks and activation of a DNA damage response. Telomere-associated proteins also regulate telomerase, the protein responsible for maintaining telomere length. Loss of telomere function results from either alteration in the capping function at telomeres, or from progressive loss of telomeric repeats necessary to maintain proper telomeric structure. Dysfunctional telomeres activate p53 to initiate cellular senescence or apoptosis to suppress tumorigenesis. However, in the absence of p53, telomere dysfunction is an important mechanism to generate chromosomal instability commonly found in human carcinomas. Telomerase is expressed in the majority of human cancers, making it an attractive therapeutic target. Emerging anti-telomerase therapies that are currently in clinical trials might prove useful against some forms of human cancers.