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Dissecting the telomere-inner nuclear membrane interface formed in meiosis

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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 Nandakumar
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.

History

Publication status

  • Published

File Version

  • Accepted version

Journal

Nature Structural and Molecular Biology

ISSN

1545-9985

Publisher

Nature Research

Issue

12

Volume

24

Page range

1064-1072

Department 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

2020-07-08

First Open Access (FOA) Date

2020-07-09

First Compliant Deposit (FCD) Date

2020-07-07

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