Structure of the Fission Yeast S. Pombe Telomeric Tpz1-Poz1-Rap1 Complex

Overview

Journal Cell Res

Specialty Cell Biology

Date 2017 Nov 22

PMID 29160296

Citations 11

Authors

Jing Xue

Hongwen Chen

Jian Wu

Miho Takeuchi

Haruna Inoue

Yanmei Liu

Hong Sun

Yong Chen

Junko Kanoh

Ming Lei

Affiliations

Soon will be listed here.

Abstract

Telomeric shelterin complex caps chromosome ends and plays a crucial role in telomere maintenance and protection. In the fission yeast Schizosaccharomyces pombe, shelterin is composed of telomeric single- and double-stranded DNA-binding protein subcomplexes Pot1-Tpz1 and Taz1-Rap1, which are bridged by their interacting protein Poz1. However, the structure of Poz1 and how Poz1 functions as an interaction hub in the shelterin complex remain unclear. Here we report the crystal structure of Poz1 in complex with Poz1-binding motifs of Tpz1 and Rap1. The crystal structure shows that Poz1 employs two different binding surfaces to interact with Tpz1 and Rap1. Unexpectedly, the structure also reveals that Poz1 adopts a dimeric conformation. Mutational analyses suggest that proper interactions between Tpz1, Poz1, and Rap1 in the shelterin core complex are required for telomere length homeostasis and heterochromatin structure maintenance at telomeres. Structural resemblance between Poz1 and the TRFH domains of other shelterin proteins in fission yeast and humans suggests a model for the evolution of shelterin proteins.

Citing Articles

Binding of the TRF2 iDDR motif to RAD50 highlights a convergent evolutionary strategy to inactivate MRN at telomeres.

Khayat F, Alshmery M, Pal M, Oliver A, Bianchi A Nucleic Acids Res. 2024; 52(13):7704-7719.

PMID: 38884214 PMC: 11260466. DOI: 10.1093/nar/gkae509.

Ccq1 restrains Mre11-mediated degradation to distinguish short telomeres from double-strand breaks.

Audry J, Zhang H, Kerr C, Berkner K, Runge K Nucleic Acids Res. 2024; 52(7):3722-3739.

PMID: 38321948 PMC: 11040153. DOI: 10.1093/nar/gkae044.

Nuclear genome organization in fungi: from gene folding to Rabl chromosomes.

Torres D, Reckard A, Klocko A, Seidl M FEMS Microbiol Rev. 2023; 47(3).

PMID: 37197899 PMC: 10246852. DOI: 10.1093/femsre/fuad021.

Telomeres and Their Neighbors.

Jenner L, Peska V, Fulneckova J, Sykorova E Genes (Basel). 2022; 13(9).

PMID: 36140830 PMC: 9498494. DOI: 10.3390/genes13091663.

Structural insights into Pot1-ssDNA, Pot1-Tpz1 and Tpz1-Ccq1 Interactions within fission yeast shelterin complex.

Sun H, Wu Z, Zhou Y, Lu Y, Lu H, Chen H PLoS Genet. 2022; 18(7):e1010308.

PMID: 35849625 PMC: 9333443. DOI: 10.1371/journal.pgen.1010308.

References

Lei M, Podell E, Cech T . Structure of human POT1 bound to telomeric single-stranded DNA provides a model for chromosome end-protection. Nat Struct Mol Biol. 2004; 11(12):1223-9. DOI: 10.1038/nsmb867. View

Wang F, Podell E, Zaug A, Yang Y, Baciu P, Cech T . The POT1-TPP1 telomere complex is a telomerase processivity factor. Nature. 2007; 445(7127):506-10. DOI: 10.1038/nature05454. View

Spink K, Ho J, Tanaka K, Watts F, Chambers A . The telomere-binding protein Taz1p as a target for modification by a SUMO-1 homologue in fission yeast. Biochem Genet. 2005; 43(3-4):103-17. DOI: 10.1007/s10528-005-1503-4. View

Ueno M, Kurokawa R, Renauld H, Watanabe K, USHIMARU T, Uritani M . Schizosaccharomyces pombe taf1+ is required for nitrogen starvation-induced sexual development and for entering the dormant GO state. Curr Genet. 2001; 38(6):307-13. DOI: 10.1007/s002940000168. View

Emsley P, Lohkamp B, Scott W, Cowtan K . Features and development of Coot. Acta Crystallogr D Biol Crystallogr. 2010; 66(Pt 4):486-501. PMC: 2852313. DOI: 10.1107/S0907444910007493. View

Bahler J, Wu J, Longtine M, Shah N, McKenzie 3rd A, Steever A . Heterologous modules for efficient and versatile PCR-based gene targeting in Schizosaccharomyces pombe. Yeast. 1998; 14(10):943-51. DOI: 10.1002/(SICI)1097-0061(199807)14:10<943::AID-YEA292>3.0.CO;2-Y. View

Hu C, Rai R, Huang C, Broton C, Long J, Xu Y . Structural and functional analyses of the mammalian TIN2-TPP1-TRF2 telomeric complex. Cell Res. 2017; 27(12):1485-1502. PMC: 5717407. DOI: 10.1038/cr.2017.144. View

Ferreira M, Cooper J . Two modes of DNA double-strand break repair are reciprocally regulated through the fission yeast cell cycle. Genes Dev. 2004; 18(18):2249-54. PMC: 517518. DOI: 10.1101/gad.315804. View

Tadeo X, Wang J, Kallgren S, Liu J, Reddy B, Qiao F . Elimination of shelterin components bypasses RNAi for pericentric heterochromatin assembly. Genes Dev. 2013; 27(22):2489-99. PMC: 3841737. DOI: 10.1101/gad.226118.113. View

10.

Court R, Chapman L, Fairall L, Rhodes D . How the human telomeric proteins TRF1 and TRF2 recognize telomeric DNA: a view from high-resolution crystal structures. EMBO Rep. 2004; 6(1):39-45. PMC: 1299224. DOI: 10.1038/sj.embor.7400314. View

11.

Kanoh J, Ishikawa F . spRap1 and spRif1, recruited to telomeres by Taz1, are essential for telomere function in fission yeast. Curr Biol. 2001; 11(20):1624-30. DOI: 10.1016/s0960-9822(01)00503-6. View

12.

Carneiro T, Khair L, Reis C, Borges V, Moser B, Nakamura T . Telomeres avoid end detection by severing the checkpoint signal transduction pathway. Nature. 2010; 467(7312):228-32. PMC: 3196630. DOI: 10.1038/nature09353. View

13.

Fairall L, CHAPMAN L, Moss H, de Lange T, Rhodes D . Structure of the TRFH dimerization domain of the human telomeric proteins TRF1 and TRF2. Mol Cell. 2001; 8(2):351-61. DOI: 10.1016/s1097-2765(01)00321-5. View

14.

Wang J, Cohen A, Letian A, Tadeo X, Moresco J, Liu J . The proper connection between shelterin components is required for telomeric heterochromatin assembly. Genes Dev. 2016; 30(7):827-39. PMC: 4826398. DOI: 10.1101/gad.266718.115. View

15.

Xin H, Liu D, Wan M, Safari A, Kim H, Sun W . TPP1 is a homologue of ciliate TEBP-beta and interacts with POT1 to recruit telomerase. Nature. 2007; 445(7127):559-62. DOI: 10.1038/nature05469. View

16.

Yamazaki H, Tarumoto Y, Ishikawa F . Tel1(ATM) and Rad3(ATR) phosphorylate the telomere protein Ccq1 to recruit telomerase and elongate telomeres in fission yeast. Genes Dev. 2012; 26(3):241-6. PMC: 3278891. DOI: 10.1101/gad.177873.111. View

17.

Miller K, Ferreira M, Cooper J . Taz1, Rap1 and Rif1 act both interdependently and independently to maintain telomeres. EMBO J. 2005; 24(17):3128-35. PMC: 1201358. DOI: 10.1038/sj.emboj.7600779. View

18.

Harland J, Chang Y, Moser B, Nakamura T . Tpz1-Ccq1 and Tpz1-Poz1 interactions within fission yeast shelterin modulate Ccq1 Thr93 phosphorylation and telomerase recruitment. PLoS Genet. 2014; 10(10):e1004708. PMC: 4199508. DOI: 10.1371/journal.pgen.1004708. View

19.

de Lange T . Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev. 2005; 19(18):2100-10. DOI: 10.1101/gad.1346005. View

20.

Armanios M, Blackburn E . The telomere syndromes. Nat Rev Genet. 2012; 13(10):693-704. PMC: 3548426. DOI: 10.1038/nrg3246. View