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

真核染色体末端 DNA 修复活动的功能和调控：对基因组稳定性的影响和后果

• 批准号: 386639-2010
• 负责人: Vodenitcharov, Momtchil
• 金额: $ 2.33万
• 依托单位: Université de Sherbrooke
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=528989
• 关键词: Functions; regulation; DNA; repair; activities

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.

遗传信息的保护和忠实传递对于细胞的正常功能和存活至关重要。线性真核染色体的物理末端，称为端粒，是真核基因组稳定性和完整性所必需的复杂核蛋白结构。端粒有两个重要功能：第一，确保染色体末端的完整复制;第二，区分染色体末端与DNA双链断裂（DSB），一种高毒性DNA损伤。DSB很容易被细胞监视机制检测到，细胞监视机制阻止细胞周期进程并将其引导到DNA修复机制。与DSB相反，染色体末端必须隐藏在DNA修复活动中。端粒的修复交易可能导致遗传信息的丢失、基因组不稳定、细胞转化以及最终的细胞死亡。巧合的是，参与DSB传感和修复的因素与端粒相关，并有助于端粒的维护。然而，目前还不清楚这些因子的常规DNA修复功能如何在端粒中调节。