减数分裂中 TERB1-TERB2-MAJIN 复合物将端粒锚定于核膜上。
The meiotic TERB1-TERB2-MAJIN complex tethers telomeres to the nuclear envelope.
机构信息
National Center for Protein Science Shanghai, State Key Laboratory of Molecular Biology, CAS Center for Excellence on Molecular Cell Science, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 200031, Shanghai, China.
Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 200011, Shanghai, China.
出版信息
Nat Commun. 2019 Feb 4;10(1):564. doi: 10.1038/s41467-019-08437-1.
During meiotic prophase I, telomeres attach to and move on the nuclear envelope (NE), regulating chromosome movement to promote homologous pairing. Meiosis-specific proteins TERB1, TERB2 and MAJIN play a key role in this process. Here, we report the crystal structures of human TERB1-TERB2 and TERB2-MAJIN subcomplexes. Specific disruption of the TERB1-TERB2 or the TERB2-MAJIN interaction in the mouse Terb2 gene abolishes the telomere attachment to the NE and causes aberrant homologous pairing and disordered synapsis. In addition, depletion of SUN1 also partially disrupts the telomere-NE connection. We propose that the telomere-TRF1-TERB1-TERB2-MAJIN-NE interaction network and the telomere-LINC complex connection are likely two separate but cooperative pathways to stably recruit telomeres to the NE in meiosis prophase I. Our work provides a molecular model of the connection between telomeres and the NE and reveals the correlation between aberrant synapsis and the defective telomere attachment to the NE.
在减数分裂前期 I 中，端粒附着在核膜（NE）上并在其上移动，调节染色体运动以促进同源配对。减数分裂特异性蛋白 TERB1、TERB2 和 MAJIN 在这个过程中发挥关键作用。在这里，我们报告了人类 TERB1-TERB2 和 TERB2-MAJIN 亚复合物的晶体结构。在小鼠 Terb2 基因中特异性破坏 TERB1-TERB2 或 TERB2-MAJIN 相互作用会导致端粒附着到 NE 上的缺失，并引起异常的同源配对和紊乱的联会。此外，SUN1 的耗竭也会部分破坏端粒-NE 连接。我们提出，端粒-TRF1-TERB1-TERB2-MAJIN-NE 相互作用网络和端粒-LINC 复合物连接可能是两种独立但协作的途径，以在减数分裂前期 I 中将端粒稳定地募集到 NE 上。我们的工作提供了端粒与 NE 之间连接的分子模型，并揭示了异常联会与端粒附着到 NE 的缺陷之间的相关性。
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