Telomeric TERB1-TRF1 interaction is crucial for male meiosis

Nat Struct Mol Biol. 2017 Dec;24(12):1073-1080. doi: 10.1038/nsmb.3496. Epub 2017 Oct 30.


During meiotic prophase, the meiosis-specific telomere-binding protein TERB1 regulates chromosome movement required for homologous pairing and recombination by interacting with the telomeric shelterin subunit TRF1. Here, we report the crystal structure of the TRF1-binding motif of human TERB1 in complex with the TRFH domain of TRF1. Notably, specific disruption of the TERB1-TRF1 interaction by a point mutation in the mouse Terb1 gene results in infertility only in males. We find that this mutation causes an arrest in the zygotene-early pachytene stage and mild telomere abnormalities of autosomes but unpaired X and Y chromosomes in pachytene, leading to massive spermatocyte apoptosis. We propose that the loss of telomere structure mediated by the TERB1-TRF1 interaction significantly affects homologous pairing of the telomere-adjacent pseudoautosomal region (PAR) of the X and Y chromosomes in mouse spermatocytes. Our findings uncover a specific mechanism of telomeres that surmounts the unique challenges of mammalian X-Y pairing in meiosis.

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Chromosome Pairing / genetics*
  • Crystallography, X-Ray
  • Gametogenesis / genetics
  • Gametogenesis / physiology
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Infertility, Male / genetics*
  • Male
  • Meiotic Prophase I / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microtubule-Associated Proteins / metabolism
  • Protein Domains
  • Spermatocytes / physiology
  • Telomere / genetics
  • Telomeric Repeat Binding Protein 1 / metabolism*


  • Carrier Proteins
  • Cell Cycle Proteins
  • Microtubule-Associated Proteins
  • SUN1 protein, mouse
  • TERB1 protein, mouse
  • Telomeric Repeat Binding Protein 1