Telomere dysfunction triggers developmentally regulated germ cell apoptosis
Telomere dysfunction triggers developmentally regulated germ cell apoptosis
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DOI：
10.1091/mbc.12.7.2023
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发表时间：
2001-07-01
影响因子：
3.3
通讯作者：
Greider, CW
中科院分区：
文献类型：
--
作者：
Hemann, MT;Rudolph, KL;Greider, CW
端粒功能障碍导致许多生物体的生育缺陷。虽然来自裂殖酵母和秀丽隐杆线虫的数据表明端粒功能障碍主要表现为减数分裂染色体分离的缺陷，但尚不清楚哺乳动物端粒功能障碍如何导致生殖细胞死亡。为了研究端粒功能障碍对哺乳动物生殖细胞发育的特异性影响，我们检测了晚代端粒酶缺失小鼠的减数分裂进程和生殖细胞凋亡。我们的研究结果表明染色体不联会和错误分离不是端粒缩短小鼠不育的原因。相反，端粒功能障碍在减数分裂开始时被识别，并且具有端粒缺陷的细胞从生殖细胞前体库中被去除。这种生殖细胞端粒监视可能是防止功能失调的端粒和染色体异常传播的重要机制。
Telomere dysfunction results in fertility defects in a number of organisms. Although data from fission yeast and Caenorhabditis elegans suggests that telomere dysfunction manifests itself primarily as defects in proper meiotic chromosome segregation, it is unclear how mammalian telomere dysfunction results in germ cell death. To investigate the specific effects of telomere dysfunction on mammalian germ cell development, we examined the meiotic progression and germ cell apoptosis in late generation telomerase null mice. Our results indicate that chromosome asynapsis and missegregation are not the cause of infertility in mice with shortened telomeres. Rather, telomere dysfunction is recognized at the onset of meiosis, and cells with telomeric defects are removed from the germ cell precursor pool. This germ cell telomere surveillance may be an important mechanism to protect against the transmission of dysfunctional telomeres and chromosomal abnormalities.