Dual roles of TRF1 in tethering telomeres to the nuclear envelope and protecting them from fusion during meiosis.
Dual roles of TRF1 in tethering telomeres to the nuclear envelope and protecting them from fusion during meiosis.
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TRF1 在将端粒束缚到核膜并保护它们在减数分裂过程中免于融合的双重作用
DOI：
10.1038/s41418-017-0037-8
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发表时间：
2018-06
影响因子：
12.4
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Wang L;Tu Z;Liu C;Liu H;Kaldis P;Chen Z;Li W
端粒完整性对于染色体稳定性不可或缺，它能防止染色体磨损及末端融合。在减数分裂过程中，端粒会附着于内核膜，并在花束期聚集形成一个高度拥挤的微环境，这就需要特定机制来保护端粒不发生融合。在此，我们证明生殖细胞中庇护蛋白复合体亚基Trf1的特异性敲除会导致精母细胞在两个不同阶段停滞。Trf1缺陷型精母细胞中端粒与核膜的附着消失，损害了同源染色体的联会和重组，从而导致类似粗线期的停滞，而减数分裂的分裂停滞可能源于因未能招募减数分裂特异性端粒相关蛋白而造成的染色体末端融合。进一步研究发现，TRF1可直接与Speedy A相互作用，Speedy A可能作为一种支架蛋白进一步招募Cdk2，从而在这一阶段保护端粒不发生融合。总之，我们的研究结果揭示了TRF1、Speedy A和Cdk2在减数分裂高度拥挤微环境中保护端粒不发生融合的新机制。
Telomeres integrity is indispensable for chromosomal stability by preventing chromosome erosion and end-to-end fusions. During meiosis, telomeres attach to the inner nuclear envelope and cluster into a highly crowded microenvironment at thebouquetstage, which requires specific mechanisms to protect the telomeres from fusion. Here, we demonstrate that germ cell-specific knockout of a shelterin complex subunit,Trf1, results in arrest of spermatocytes at two different stages. The obliterated telomere-nuclear envelope attachment inTrf1-deficient spermatocytes impairs homologue synapsis and recombination, resulting in a pachytene-like arrest, while the meiotic division arrest might stem from chromosome end-to-end fusion due to the failure of recruiting meiosis specific telomere associated proteins. Further investigations uncovered that TRF1 could directly interact with Speedy A, and Speedy A might work as a scaffold protein to further recruit Cdk2, thus protecting telomeres from fusion at this stage. Together, our results reveal a novel mechanism of TRF1, Speedy A, and Cdk2 in protecting telomere from fusion in a highly crowded microenvironment during meiosis.
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