Wang, L., Tu, Z., Liu, C., Liu, H., Kaldis, P., Chen, Z., & Li, W. (2018). Dual roles of TRF1 in tethering telomeres to the nuclear envelope and protecting them from fusion during meiosis. Cell Death & Differentiation, 25(6), 1174–1188. doi:10.1038/s41418-017-0037-8
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
License type:
Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
Funding Info:
This research is supported by core funding from: A*STAR, Biomedical Research Council
Grant Reference no. :
Overseas Fund:-
1) National key R&D program of China (Grant No. 2016YFA0500901),
2) National Nature Science of China (Grant No. 31471277 and 91649202)