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Nat Struct Mol Biol. 2017 Dec;24(12):1064-1072. doi: 10.1038/nsmb.3493. Epub 2017 Oct 30.

Dissecting the telomere-inner nuclear membrane interface formed in meiosis.

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Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA.
Program in Chemical Biology, University of Michigan, Ann Arbor, Michigan, USA.
University of Tokyo, Institute of Molecular and Cellular Biosciences, Laboratory of Chromosome Dynamics, Tokyo, Japan.
Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.


Tethering telomeres to the inner nuclear membrane (INM) allows homologous chromosome pairing during meiosis. The meiosis-specific protein TERB1 binds the telomeric protein TRF1 to establish telomere-INM connectivity and is essential for mouse fertility. Here we solve the structure of the human TRF1-TERB1 interface to reveal the structural basis for telomere-INM linkage. Disruption of this interface abrogates binding and compromises telomere-INM attachment in mice. An embedded CDK-phosphorylation site within the TRF1-binding region of TERB1 provides a mechanism for cap exchange, a late-pachytene phenomenon involving the dissociation of the TRF1-TERB1 complex. Indeed, further strengthening this interaction interferes with cap exchange. Finally, our biochemical analysis implicates distinct complexes for telomere-INM tethering and chromosome-end protection during meiosis. Our studies unravel the structure, stoichiometry, and physiological implications underlying telomere-INM tethering, thereby providing unprecedented insights into the unique function of telomeres in meiosis.

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