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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.

Author information

1
Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA.
2
Program in Chemical Biology, University of Michigan, Ann Arbor, Michigan, USA.
3
University of Tokyo, Institute of Molecular and Cellular Biosciences, Laboratory of Chromosome Dynamics, Tokyo, Japan.
4
Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.

Abstract

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.

PMID:
29083414
PMCID:
PMC5755706
DOI:
10.1038/nsmb.3493
[Indexed for MEDLINE]
Free PMC Article

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