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Title: Dissecting the telomere–inner nuclear membrane interface formed in meiosis

Abstract

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.

Authors:
; ; ; ; ; ORCiD logo; ORCiD logo
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
OTHER U.S. STATESNIHOTHER
OSTI Identifier:
1419883
Resource Type:
Journal Article
Resource Relation:
Journal Name: Nature Structural & Molecular Biology; Journal Volume: 24; Journal Issue: 12
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Pendlebury, Devon F., Fujiwara, Yasuhiro, Tesmer, Valerie M., Smith, Eric M., Shibuya, Hiroki, Watanabe, Yoshinori, and Nandakumar, Jayakrishnan. Dissecting the telomere–inner nuclear membrane interface formed in meiosis. United States: N. p., 2017. Web. doi:10.1038/nsmb.3493.
Pendlebury, Devon F., Fujiwara, Yasuhiro, Tesmer, Valerie M., Smith, Eric M., Shibuya, Hiroki, Watanabe, Yoshinori, & Nandakumar, Jayakrishnan. Dissecting the telomere–inner nuclear membrane interface formed in meiosis. United States. doi:10.1038/nsmb.3493.
Pendlebury, Devon F., Fujiwara, Yasuhiro, Tesmer, Valerie M., Smith, Eric M., Shibuya, Hiroki, Watanabe, Yoshinori, and Nandakumar, Jayakrishnan. Mon . "Dissecting the telomere–inner nuclear membrane interface formed in meiosis". United States. doi:10.1038/nsmb.3493.
@article{osti_1419883,
title = {Dissecting the telomere–inner nuclear membrane interface formed in meiosis},
author = {Pendlebury, Devon F. and Fujiwara, Yasuhiro and Tesmer, Valerie M. and Smith, Eric M. and Shibuya, Hiroki and Watanabe, Yoshinori and Nandakumar, Jayakrishnan},
abstractNote = {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.},
doi = {10.1038/nsmb.3493},
journal = {Nature Structural & Molecular Biology},
number = 12,
volume = 24,
place = {United States},
year = {Mon Oct 30 00:00:00 EDT 2017},
month = {Mon Oct 30 00:00:00 EDT 2017}
}