Abstract
Chromosomes pair and synapse with their homologous partners to segregate correctly at the first meiotic division. Association of telomeres with the LINC (Linker of Nucleoskeleton and Cytoskeleton) complex composed of SUN1 and KASH5 enables telomere-led chromosome movements and telomere bouquet formation, facilitating precise pairwise alignment of homologs. Here, we identify a direct interaction between SUN1 and Speedy A (SPDYA) and determine the crystal structure of human SUN1-SPDYA-CDK2 ternary complex. Analysis of meiosis prophase I process in SPDYA-binding-deficient SUN1 mutant mice reveals that the SUN1-SPDYA interaction is required for the telomere-LINC complex connection and the assembly of a ring-shaped telomere supramolecular architecture at the nuclear envelope, which is critical for efficient homologous pairing and synapsis. Overall, our results provide structural insights into meiotic telomere structure that is essential for meiotic prophase I progression.
Highlights
Chromosomes pair and synapse with their homologous partners to segregate correctly at the first meiotic division
We identify a direct interaction between SUN1 and Speedy A (SPDYA), determine the crystal structure of the SUN1–SPDYA–CDK2 ternary complex, and provide in vivo evidence that SUN1–SPDYAmediated LINC–telomere connection is essential for the assembly of a nuclear envelope (NE)-attached ring-shaped telomeric supramolecular complex that plays an essential role in meiotic prophase I progression
To understand how the LINC complex is connected to telomeres in meiosis, we employed yeast two-hybrid (Y2H) interaction analysis to systematically examine the potential interactions between SUN1 with telomeric shelterin proteins and meiotic factors that have been reported to play important roles at telomeres[13,14,15,16,17,18]
Summary
Chromosomes pair and synapse with their homologous partners to segregate correctly at the first meiotic division. Knockout of either SPDYA or CDK2 results in the same meiotic defects, including accumulated nucleoplasmic telomeres and prophase arrest with aberrant synapsis, implying that SPDYA and CDK2 likely function together in regulating telomere–INM attachment, and are critical for homolog pairing in early prophase I16–19. We identify a direct interaction between SUN1 and SPDYA, determine the crystal structure of the SUN1–SPDYA–CDK2 ternary complex, and provide in vivo evidence that SUN1–SPDYAmediated LINC–telomere connection is essential for the assembly of a nuclear envelope (NE)-attached ring-shaped telomeric supramolecular complex that plays an essential role in meiotic prophase I progression.
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