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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / isolation & purification
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Cell Cycle Proteins / metabolism*
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Cell Cycle Proteins / ultrastructure
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Cell Line, Tumor
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Crystallography, X-Ray
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Cyclin-Dependent Kinase 2 / genetics
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Cyclin-Dependent Kinase 2 / isolation & purification
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Cyclin-Dependent Kinase 2 / metabolism
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Cyclin-Dependent Kinase 2 / ultrastructure
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Female
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HEK293 Cells
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Humans
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Male
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Meiotic Prophase I*
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Membrane Proteins / genetics
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Membrane Proteins / isolation & purification
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Membrane Proteins / metabolism*
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Membrane Proteins / ultrastructure
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Mice
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Mice, Transgenic
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Microtubule-Associated Proteins / genetics
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Microtubule-Associated Proteins / isolation & purification
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Microtubule-Associated Proteins / metabolism*
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Microtubule-Associated Proteins / ultrastructure
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Mutation
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Nuclear Proteins / genetics
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Nuclear Proteins / isolation & purification
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Nuclear Proteins / metabolism*
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Nuclear Proteins / ultrastructure
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Recombinant Proteins / genetics
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Recombinant Proteins / isolation & purification
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Recombinant Proteins / metabolism
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Recombinant Proteins / ultrastructure
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Telomere / metabolism*
Substances
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Cell Cycle Proteins
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Membrane Proteins
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Microtubule-Associated Proteins
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Nuclear Proteins
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Recombinant Proteins
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SPDYA protein, human
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SUN1 protein, human
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SUN1 protein, mouse
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Spy1 protein, mouse
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CDK2 protein, human
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Cyclin-Dependent Kinase 2