Structural highlights
Function
TERB1_HUMAN Meiosis-specific telomere-associated protein involved in meiotic telomere attachment to the nucleus inner membrane, a crucial step for homologous pairing and synapsis. Component of the MAJIN-TERB1-TERB2 complex, which promotes telomere cap exchange by mediating attachment of telomeric DNA to the inner nuclear membrane and replacement of the protective cap of telomeric chromosomes: in early meiosis, the MAJIN-TERB1-TERB2 complex associates with telomeric DNA and the shelterin/telosome complex. During prophase, the complex matures and promotes release of the shelterin/telosome complex from telomeric DNA. In the MAJIN-TERB1-TERB2 complex, TERB1 probably mediates association with the shelterin/telosome complex via interaction with TERF1, promoting priming telomeric DNA attachment'. Promotes telomere association with the nuclear envelope and deposition of the SUN-KASH/LINC complex. Also recruits cohesin to telomeres to develop structural rigidity.[UniProtKB:Q8C0V1]
Publication Abstract from PubMed
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.
Dissecting the telomere-inner nuclear membrane interface formed in meiosis.,Pendlebury DF, Fujiwara Y, Tesmer VM, Smith EM, Shibuya H, Watanabe Y, Nandakumar J Nat Struct Mol Biol. 2017 Oct 30. doi: 10.1038/nsmb.3493. PMID:29083414[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Pendlebury DF, Fujiwara Y, Tesmer VM, Smith EM, Shibuya H, Watanabe Y, Nandakumar J. Dissecting the telomere-inner nuclear membrane interface formed in meiosis. Nat Struct Mol Biol. 2017 Oct 30. doi: 10.1038/nsmb.3493. PMID:29083414 doi:http://dx.doi.org/10.1038/nsmb.3493
