Dissecting the telomere-inner nuclear membrane interface formed in meiosis

Pendlebury, Devon F, Fujiwara, Yasuhiro, Tesmer, Valerie M, Smith, Eric M, Shibuya, Hiroki, Watanabe, Yoshinori and Nandakumar, Jayakrishnan (2017) Dissecting the telomere-inner nuclear membrane interface formed in meiosis. Nature Structural and Molecular Biology, 24 (12). pp. 1064-1072. ISSN 1545-9985

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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.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Research Centres and Groups: Genome Damage and Stability Centre
Depositing User: Yoshinori Watanabe
Date Deposited: 08 Jul 2020 09:45
Last Modified: 09 Jul 2020 08:00
URI: http://sro.sussex.ac.uk/id/eprint/92409

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