and 31270787 to Z.Z.) and the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20181711 to J.W.). This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: The atomic models of Pot1DBD-Tel18, Pot1OB3-Tpz1PIM and Ccq1TAD-Tpz1CBM were deposited in Protein Data Bank with accession codes 7CUH, 7CUI and 7CUJ, respectively.įunding: This work was supported by grants from the Ministry of Science and Technology of China (2018YFA0107004 to M.L.), the National Natural Science Foundation of China (31930063 to M.L. Received: MaAccepted: JPublished: July 18, 2022Ĭopyright: © 2022 Sun et al. PLoS Genet 18(7):Įditor: Hiroki Shibuya, Goteborgs Universitet, SWEDEN (2022) Structural insights into Pot1-ssDNA, Pot1-Tpz1 and Tpz1-Ccq1 Interactions within fission yeast shelterin complex. These findings provide an integrated model depicting the assembly mechanism of the shelterin complex at telomeres and its multiple roles in telomere biology.Ĭitation: Sun H, Wu Z, Zhou Y, Lu Y, Lu H, Chen H, et al. pombe degenerate telomeric sequences by Pot1, but also for the essential function of the Tpz1-Ccq1 interaction in Ccq1 recruitment to telomeres for telomere maintenance and telomeric heterochromatin formation. Here, by determining the crystal structures of the telomeric overhang binding Pot1 DBD-ssDNA, Pot1 372-555-Tpz1 185-212 and Tpz1 425-470-Ccq1 123-439 subcomplexes, we provide structural basis not only for the recognition of S. Although individual OB-fold subdomains structures have been characterized, structural information about the complete Pot1 DBD bound to telomeric repeats with spacers remains to be revealed. In fission yeast, structures of the shelterin dsDNA-binding protein subcomplex Taz1-Rap1 and the bridge subcomplex Tpz1-Poz1-Rap1 are available. However, the highly flexible nature of shelterin complex has greatly impeded our structural and functional understanding for this important complex. An evolutionarily conserved multiple-protein complex called shelterin plays versatile roles in telomere homeostasis regulation, end protection and heterochromatin establishment. The telomere structure is essential for the maintenance of genome integrity and stability, and telomere dysfunction has been linked to human development, aging, cancer and a variety of degenerative diseases. Telomeres, composed of repetitive DNA sequences and specialized proteins, are protective structures at the ends of linear chromosomes. Overall, our findings provide valuable structural information regarding interactions within fission yeast shelterin complex at 3’ ss telomeric overhang. Our analyses of Tpz1-Ccq1 reveal structural basis for the essential role of the Tpz1-Ccq1 interaction in telomere recruitment of Ccq1 that is required for telomere maintenance and telomeric heterochromatin formation. The structure of Pot1 DBD-DNA unveils how Pot1 recognizes S. Here, we report the crystal structures of Pot1 DBD-single-stranded-DNA, Pot1 372-555-Tpz1 185-212 and Tpz1 425-470-Ccq1 123-439 complexes and propose an integrated model depicting the assembly mechanism of the shelterin complex at telomeres. pombe shelterin is recruited to telomeres to function as an interacting hub. Moreover, structural information about the Tpz1-Ccq1 interaction requires to be revealed for understanding how the specific component Ccq1 of S. While individual structures of the two DNA-binding OB folds of Pot1 (Pot1 OB1-GGTTAC and Pot1 OB2-GGTTACGGT) are available, structural insight into recognition of telomeric repeats with spacers by the complete DNA-binding domain (Pot1 DBD) remains an open question. In fission yeast Schizosaccharomyces pombe, shelterin consists of telomeric single- and double-stranded DNA-binding modules Pot1-Tpz1 and Taz1-Rap1 connected by Poz1, and a specific component Ccq1. The conserved shelterin complex caps chromosome ends to protect telomeres and regulate telomere replication.
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