Functions and regulation of DNA repair activities at eukaryotic chromosome ends: impact and consequences for genome stability

保护和忠实地传递遗传信息对于细胞的正常功能和生存至关重要。线性真核染色体的物理末端称为端粒，是对真核基因组的稳定性和完整性至关重要的复杂核蛋白结构。端粒具有两个重要的功能：第一，它们确保染色体末端的完全复制；第二，它们将染色体末端与DNA双链断裂(DSB)区分开来，双链断裂是一种剧毒的DNA损伤。DSB很容易被细胞监测机制检测到，该机制阻止细胞周期进程，并将它们引导到DNA修复机制。与DSB不同的是，染色体末端必须隐藏在DNA修复活动之外。端粒的修复交易可能导致遗传信息的丢失、基因组的不稳定、细胞的转化，并最终导致细胞死亡。矛盾的是，参与DSB感知和修复的因子与端粒相关，并有助于端粒的维持。然而，目前还不清楚这些因子的常规DNA修复功能是如何在端粒上调节的。

The protection and faithful transmission of genetic information is essential for adequate cell function and survival. The physical ends of linear eukaryotic chromosomes, called telomeres, are complex nucleoprotein structures essential for the stability and integrity of the eukaryotic genome. Telomeres fulfill two important functions: first, they assure complete replication of chromosome termini and, second, they distinguish chromosomal ends from DNA double stranded breaks (DSB), a type of highly toxic DNA lesions. DSB are readily detected by cellular surveillance mechanisms that arrest cell cycle progression and channel them to DNA repair machinery. In contrast to DSB, chromosomal ends must be hidden form DNA repair activities. Repair transactions at telomeres can lead to loss of genetic information, genome instability, cellular transformation and, ultimately, cell death. Paradoxically, factors involved in DSB sensing and repair associate with telomeres and assist in telomere maintenance. However, it is unclear how the routine DNA repair functions of these factors are regulated at telomeres.