Dissecting the telomere-inner nuclear membrane interface formed in meiosis

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


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.

MeSH terms

  • Animals
  • Binding Sites / genetics
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Chromosome Pairing
  • Meiosis / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nuclear Envelope / metabolism*
  • Phosphorylation
  • Protein Binding / physiology
  • Telomere / metabolism*
  • Telomeric Repeat Binding Protein 1 / metabolism*
  • rap1 GTP-Binding Proteins / metabolism


  • Carrier Proteins
  • Cell Cycle Proteins
  • TERB1 protein, mouse
  • Telomeric Repeat Binding Protein 1
  • Rap1 protein, mouse
  • rap1 GTP-Binding Proteins