Pendlebury_Watanabe_79.pdf (8.68 MB)
Dissecting the telomere-inner nuclear membrane interface formed in meiosis
journal contribution
posted on 2023-06-07, 07:28 authored by Devon F Pendlebury, Yasuhiro Fujiwara, Valerie M Tesmer, Eric M Smith, Hiroki Shibuya, Yoshinori Watanabe, Jayakrishnan NandakumarTethering 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.
History
Publication status
- Published
File Version
- Accepted version
Journal
Nature Structural and Molecular BiologyISSN
1545-9985Publisher
Nature ResearchExternal DOI
Issue
12Volume
24Page range
1064-1072Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Research groups affiliated with
- Genome Damage and Stability Centre Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2020-07-08First Open Access (FOA) Date
2020-07-09First Compliant Deposit (FCD) Date
2020-07-07Usage metrics
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