Division of Molecular Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Cell Cycle. 2012 Apr 15;11(8):1524-34. doi: 10.4161/cc.19847.
Telomeres help maintain genome integrity by protecting natural chromosome ends from being recognized as damaged DNA. When telomeres become dysfunctional, they limit replicative lifespan and prevent outgrowth of potentially cancerous cells by activating a DNA damage response that forces cells into senescence or apoptosis. On the other hand, chromosome ends devoid of proper telomere protection are subject to DNA repair activities that cause end-to-end fusions and, when cells divide, extensive genomic instability that can promote cancer. While telomeres represent unique chromatin structures with important roles in cancer and aging, we have limited understanding of the way telomeres and the response to their malfunction are controlled at the level of chromatin. Accumulating evidence indicates that different types of posttranslational modifications act in both telomere maintenance and the response to telomere uncapping. Here, we discuss the latest insights on posttranslational control of telomeric chromatin, with emphasis on ubiquitylation and SUMOylation events.
端粒通过保护天然染色体末端不被识别为受损 DNA，来帮助维持基因组完整性。当端粒失去功能时，它们会通过激活一种 DNA 损伤反应，迫使细胞进入衰老或凋亡，从而限制细胞的复制寿命并阻止潜在癌变细胞的生长。另一方面，没有适当端粒保护的染色体末端会受到导致端到端融合的 DNA 修复活动的影响，并且在细胞分裂时，会出现广泛的基因组不稳定性，从而促进癌症的发生。虽然端粒代表着在癌症和衰老中具有重要作用的独特染色质结构，但我们对端粒及其对功能失调的反应在染色质水平上的控制方式的理解有限。越来越多的证据表明，不同类型的翻译后修饰在端粒维持和端粒去帽反应中都有作用。在这里，我们讨论了端粒染色质翻译后控制的最新见解，重点介绍了泛素化和 SUMO 化事件。
