Abstract
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.
Highlights
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
KASH5 interacts with microtubules via dynein–dynactin[22,32], accounting for the autonomous movements of chromosome ends along stationary microtubule tracts that have been visualised in meiotic prophase mouse spermatocytes[6,7]
The MAJIN–TERB2–TERB1 meiotic telomere complex integrates functions of the linker of nucleoskeleton and cytoskeleton (LINC) and shelterin complexes to physically connect telomere ends to the cytoskeleton
Summary
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. In meiotic prophase I, the nuclear lamina undergoes an extensive reorganisation[27] and LINC complexes become associated with the meiotic telomere complex[28], transmitting cytoskeletal forces to meiotic telomere end assemblies that are freely mobile within the plane of the nuclear envelope These movements are achieved by the partially redundant universally expressed SUN domain proteins SUN1 and SUN229–31, and a meiosis-specific KASH domain protein, KASH5, which is essential for meiotic telomere attachments[22,32]. Meiotic telomere complex components MAJIN, TERB1 and TERB2 are essential for fertility; their individual disruption in a Microtubules
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