Program in mammalian telomere biology

哺乳动物端粒生物学项目

• 批准号: RGPIN-2017-04871
• 负责人: Riabowol, Karl
• 金额: $ 3.5万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=630531
• 关键词: Program; mammalian; telomere; biology

The ends of mammalian chromosomes contain variable numbers of TTAGGG repeats. In many species this telomeric DNA is lost due to the end replication problem, as normal somatic cells replicate. When cells lose sufficient telomeric DNA, a DNA damage signal is generated, activating the ATM kinase and p53 transcription factor to block the cell cycle and induce cell replicative senescence. Senescence is thought to serve as a barrier to cell immortality and abnormal cell growth since it limits cell replicative capacity. However, short telomeres also result in genetic instability leading to a variety of diseases and large correlational studies have linked short telomeres to high rates of cell transformation. Short telomeres are also associated with early mortality, suggesting that telomere length might contribute to determining lifespan. Studies of monozygotic and dizygotic twins and elderly populations have yielded conflicting results, leaving the question of whether telomere length per se affects life span, controversial.

哺乳动物染色体的末端包含不同数量的TTAGGG重复序列。在许多物种中，当正常体细胞复制时，端粒DNA由于末端复制问题而丢失。当细胞失去足够的端粒DNA时，产生DNA损伤信号，激活ATM激酶和p53转录因子，阻断细胞周期，诱导细胞复制性衰老。衰老被认为是细胞不朽和细胞异常生长的障碍，因为它限制了细胞的复制能力。然而，短端粒也会导致遗传不稳定，导致各种疾病，大量相关研究已将短端粒与高细胞转化率联系起来。短端粒也与早期死亡有关，这表明端粒长度可能决定寿命。对同卵双胞胎和异卵双胞胎以及老年人群的研究产生了相互矛盾的结果，使得端粒长度本身是否影响寿命的问题备受争议。