Mammalian Ku86 mediates chromosomal fusions and apoptosis caused by critically short telomeres
Mammalian Ku86 mediates chromosomal fusions and apoptosis caused by critically short telomeres
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DOI：
10.1093/emboj/21.9.2207
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发表时间：
2002-05-01
期刊：
影响因子：
11.4
通讯作者：
Blasco, MA
中科院分区：
文献类型：
--
作者：
Espejel, S;Franco, S;Blasco, MA
在这里，我们分析Ku86和端粒酶在哺乳动物端粒的功能之间的相互作用，通过研究小鼠这两种蛋白质的缺陷。我们表明，Ku86的情况下，防止端到端的染色体融合，导致端粒缩短端粒酶缺陷小鼠的关键。此外，Ku86缺陷拯救了这些小鼠中由短端粒引发的雄性早期生殖细胞凋亡。总之，这些发现确定了Ku86在介导短端粒引发的染色体不稳定性和细胞凋亡中的作用。此外，我们在这里表明，Ku86缺陷导致端粒依赖性端粒延长和端粒活性细胞中染色体随机对的融合，这表明Ku86使正常长度的端粒不易被端粒酶介导的端粒延长和DNA修复活性所接近的模型。
Here we analyze the functional interaction between Ku86 and telomerase at the mammalian telomere by studying mice deficient for both proteins. We show that absence of Ku86 prevents the end-to-end chromosomal fusions that result from critical telomere shortening in telomerase-deficient mice. In addition, Ku86 deficiency rescues the male early germ cell apoptosis triggered by short telomeres in these mice. Together, these findings define a role for Ku86 in mediating chromosomal instability and apoptosis triggered by short telomeres. In addition, we show here that Ku86 deficiency results in telomerase-dependent telomere elongation and in the fusion of random pairs of chromosomes in telomerase-proficient cells, suggesting a model in which Ku86 keeps normal-length telomeres less accessible to telomerase- mediated telomere lengthening and to DNA repair activities.