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Title: Dual Roles of TRF1 in Tethering Telomeres to the Nuclear Envelope and Protecting Them from Fusion During Meiosis
Author: Lina Wang, Zhaowei Tu, Chao Liu, Hongbin Liu, Philipp Kaldis, Zijiang Chen, Wei Li
Abstract: 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 the bouquet stage, 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 in Trf1-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.
Corresponding author: Zijiang Chen, Wei Li
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PubYear: 2018
Issue: DOI: 10.1038/s41418-017-0037-8
Journal: Cell Death and Differentiation
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URL: https://www.nature.com/articles/s41418-017-0037-8