The meiotic TERB1-TERB2-MAJIN complex tethers telomeres to the nuclear envelope

作者：Yan Wang, Yanyan Chen, Juan Chen, Lijun Wang, Leitong Nie, Juanjuan Long, Haishuang Chang, Jian Wu, Chenhui Huang, Ming Lei · 发表于：Nature Communications · 年份：2019 · DOI：10.1038/s41467-019-08437-1 · 被引用次数：55 · 研究领域：Nuclear Structure and Function、DNA Repair Mechanisms、Telomeres, Telomerase, and Senescence

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.