Institute for Cell and Molecular Biosciences, Faculty of Medical Sciences, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
Department of Cell and Developmental Biology, Biocenter, University of Würzburg, D-97074, Würzburg, Germany.
Nat Commun. 2018 Dec 17;9(1):5355. doi: 10.1038/s41467-018-07794-7.
Meiotic chromosomes undergo rapid prophase movements, which are thought to facilitate the formation of inter-homologue recombination intermediates that underlie synapsis, crossing over and segregation. The meiotic telomere complex (MAJIN, TERB1, TERB2) tethers telomere ends to the nuclear envelope and transmits cytoskeletal forces via the LINC complex to drive these rapid movements. Here, we report the molecular architecture of the meiotic telomere complex through the crystal structure of MAJIN-TERB2, together with light and X-ray scattering studies of wider complexes. The MAJIN-TERB2 2:2 hetero-tetramer binds strongly to DNA and is tethered through long flexible linkers to the inner nuclear membrane and two TRF1-binding 1:1 TERB2-TERB1 complexes. Our complementary structured illumination microscopy studies and biochemical findings reveal a telomere attachment mechanism in which MAJIN-TERB2-TERB1 recruits telomere-bound TRF1, which is then displaced during pachytene, allowing MAJIN-TERB2-TERB1 to bind telomeric DNA and form a mature attachment plate.
减数分裂染色体经历快速的前期运动，这些运动被认为有助于形成同源重组中间体，为联会、交叉和分离奠定基础。减数分裂端粒复合物（MAJIN、TERB1、TERB2）将端粒末端与核膜连接，并通过 LINC 复合物传递细胞骨架力，以驱动这些快速运动。在这里，我们通过 MAJIN-TERB2 的晶体结构以及更广泛复合物的光和 X 射线散射研究报告了减数分裂端粒复合物的分子结构。MAJIN-TERB2 2:2 异四聚体与 DNA 结合紧密，并通过长的柔性接头与内核膜和两个 TRF1 结合 1:1 TERB2-TERB1 复合物连接。我们的互补结构照明显微镜研究和生化发现揭示了一种端粒附着机制，其中 MAJIN-TERB2-TERB1 招募端粒结合的 TRF1，然后在粗线期被置换，从而允许 MAJIN-TERB2-TERB1 结合端粒 DNA 并形成成熟的附着盘。
