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Publication : Telomeric TERB1-TRF1 interaction is crucial for male meiosis.

First Author  Long J Year  2017
Journal  Nat Struct Mol Biol Volume  24
Issue  12 Pages  1073-1080
PubMed ID  29083416 Mgi Jnum  J:286164
Mgi Id  MGI:6390656 Doi  10.1038/nsmb.3496
Citation  Long J, et al. (2017) Telomeric TERB1-TRF1 interaction is crucial for male meiosis. Nat Struct Mol Biol 24(12):1073-1080
abstractText  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.
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