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Structural Insights into Yeast Telomerase Recruitment to Telomeres.

Chen H, Xue J, Churikov D, Hass EP, Shi S, Lemon LD, Luciano P, Bertuch AA, Zappulla DC, Géli V, Wu J, Lei M
Cell 172 331-343.e13 (2018)
Related entries: 5y58, 5y59

Cited: 48 times
EuropePMC logo PMID: 29290466

Abstract

Telomerase maintains chromosome ends from humans to yeasts. Recruitment of yeast telomerase to telomeres occurs through its Ku and Est1 subunits via independent interactions with telomerase RNA (TLC1) and telomeric proteins Sir4 and Cdc13, respectively. However, the structures of the molecules comprising these telomerase-recruiting pathways remain unknown. Here, we report crystal structures of the Ku heterodimer and Est1 complexed with their key binding partners. Two major findings are as follows: (1) Ku specifically binds to telomerase RNA in a distinct, yet related, manner to how it binds DNA; and (2) Est1 employs two separate pockets to bind distinct motifs of Cdc13. The N-terminal Cdc13-binding site of Est1 cooperates with the TLC1-Ku-Sir4 pathway for telomerase recruitment, whereas the C-terminal interface is dispensable for binding Est1 in vitro yet is nevertheless essential for telomere maintenance in vivo. Overall, our results integrate previous models and provide fundamentally valuable structural information regarding telomere biology.

Reviews - 5y5a mentioned but not cited (1)

  1. Telomerase structures and regulation: shedding light on the chromosome end. Nguyen THD, Collins K, Nogales E. Curr Opin Struct Biol 55 185-193 (2019)

Articles - 5y5a mentioned but not cited (1)

  1. Structural Insights into Yeast Telomerase Recruitment to Telomeres. Chen H, Xue J, Churikov D, Hass EP, Shi S, Lemon LD, Luciano P, Bertuch AA, Zappulla DC, Géli V, Wu J, Lei M. Cell 172 331-343.e13 (2018)


Reviews citing this publication (15)

  1. Long non-coding RNAs: definitions, functions, challenges and recommendations. Mattick JS, Amaral PP, Carninci P, Carpenter S, Chang HY, Chen LL, Chen R, Dean C, Dinger ME, Fitzgerald KA, Gingeras TR, Guttman M, Hirose T, Huarte M, Johnson R, Kanduri C, Kapranov P, Lawrence JB, Lee JT, Mendell JT, Mercer TR, Moore KJ, Nakagawa S, Rinn JL, Spector DL, Ulitsky I, Wan Y, Wilusz JE, Wu M. Nat Rev Mol Cell Biol 24 430-447 (2023)
  2. ATM, ATR and DNA-PKcs kinases-the lessons from the mouse models: inhibition ≠ deletion. Menolfi D, Zha S. Cell Biosci 10 8 (2020)
  3. Roles of Telomere Biology in Cell Senescence, Replicative and Chronological Ageing. Liu J, Wang L, Wang Z, Liu JP. Cells 8 E54 (2019)
  4. The landscape of aging. Cai Y, Song W, Li J, Jing Y, Liang C, Zhang L, Zhang X, Zhang W, Liu B, An Y, Li J, Tang B, Pei S, Wu X, Liu Y, Zhuang CL, Ying Y, Dou X, Chen Y, Xiao FH, Li D, Yang R, Zhao Y, Wang Y, Wang L, Li Y, Ma S, Wang S, Song X, Ren J, Zhang L, Wang J, Zhang W, Xie Z, Qu J, Wang J, Xiao Y, Tian Y, Wang G, Hu P, Ye J, Sun Y, Mao Z, Kong QP, Liu Q, Zou W, Tian XL, Xiao ZX, Liu Y, Liu JP, Song M, Han JJ, Liu GH. Sci China Life Sci 65 2354-2454 (2022)
  5. Telomere Replication: Solving Multiple End Replication Problems. Bonnell E, Pasquier E, Wellinger RJ. Front Cell Dev Biol 9 668171 (2021)
  6. The Multifaceted Roles of Ku70/80. Zahid S, Seif El Dahan M, Iehl F, Fernandez-Varela P, Le Du MH, Ropars V, Charbonnier JB. Int J Mol Sci 22 4134 (2021)
  7. Structural Biology of Telomerase. Wang Y, Sušac L, Feigon J. Cold Spring Harb Perspect Biol 11 a032383 (2019)
  8. How long does telomerase extend telomeres? Regulation of telomerase release and telomere length homeostasis. Tomita K. Curr Genet 64 1177-1181 (2018)
  9. The Ku complex: recent advances and emerging roles outside of non-homologous end-joining. Abbasi S, Parmar G, Kelly RD, Balasuriya N, Schild-Poulter C. Cell Mol Life Sci 78 4589-4613 (2021)
  10. Telomere Maintenance in Pediatric Cancer. Ackermann S, Fischer M. Int J Mol Sci 20 E5836 (2019)
  11. Telomeres and Cancer. Fan HC, Chang FW, Tsai JD, Lin KM, Chen CM, Lin SZ, Liu CA, Harn HJ. Life (Basel) 11 1405 (2021)
  12. Yeast Telomerase RNA Flexibly Scaffolds Protein Subunits: Results and Repercussions. Zappulla DC. Molecules 25 E2750 (2020)
  13. CST-Polα/Primase: the second telomere maintenance machine. Cai SW, de Lange T. Genes Dev 37 555-569 (2023)
  14. Maturation and shuttling of the yeast telomerase RNP: assembling something new using recycled parts. Bartle L, Vasianovich Y, Wellinger RJ. Curr Genet 68 3-14 (2022)
  15. Post-Transcriptional and Post-Translational Modifications in Telomerase Biogenesis and Recruitment to Telomeres. Shepelev N, Dontsova O, Rubtsova M. Int J Mol Sci 24 5027 (2023)

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  1. DNA-PKcs has KU-dependent function in rRNA processing and haematopoiesis. Shao Z, Flynn RA, Crowe JL, Zhu Y, Liang J, Jiang W, Aryan F, Aoude P, Bertozzi CR, Estes VM, Lee BJ, Bhagat G, Zha S, Calo E. Nature 579 291-296 (2020)
  2. Mechanism of efficient double-strand break repair by a long non-coding RNA. Thapar R, Wang JL, Hammel M, Ye R, Liang K, Sun C, Hnizda A, Liang S, Maw SS, Lee L, Villarreal H, Forrester I, Fang S, Tsai MS, Blundell TL, Davis AJ, Lin C, Lees-Miller SP, Strick TR, Tainer JA. Nucleic Acids Res 48 10953-10972 (2020)
  3. Chromosome-specific telomere lengths and the minimal functional telomere revealed by nanopore sequencing. Sholes SL, Karimian K, Gershman A, Kelly TJ, Timp W, Greider CW. Genome Res 32 616-628 (2022)
  4. Structural insights into telomere protection and homeostasis regulation by yeast CST complex. Ge Y, Wu Z, Chen H, Zhong Q, Shi S, Li G, Wu J, Lei M. Nat Struct Mol Biol 27 752-762 (2020)
  5. Stability and nuclear localization of yeast telomerase depend on protein components of RNase P/MRP. Garcia PD, Leach RW, Wadsworth GM, Choudhary K, Li H, Aviran S, Kim HD, Zakian VA. Nat Commun 11 2173 (2020)
  6. LRIK interacts with the Ku70-Ku80 heterodimer enhancing the efficiency of NHEJ repair. Wang D, Zhou Z, Wu E, Ouyang C, Wei G, Wang Y, He D, Cui Y, Zhang D, Chen X, Reed SH, Luo J, Chen R. Cell Death Differ 27 3337-3353 (2020)
  7. Functional diversification of Paramecium Ku80 paralogs safeguards genome integrity during precise programmed DNA elimination. Abello A, Régnier V, Arnaiz O, Le Bars R, Bétermier M, Bischerour J. PLoS Genet 16 e1008723 (2020)
  8. TERribly Difficult: Searching for Telomerase RNAs in Saccharomycetes. Waldl M, Thiel BC, Ochsenreiter R, Holzenleiter A, de Araujo Oliveira JV, Walter MEMT, Wolfinger MT, Stadler PF. Genes (Basel) 9 E372 (2018)
  9. Ligand binding characteristics of the Ku80 von Willebrand domain. Kim K, Min J, Kirby TW, Gabel SA, Pedersen LC, London RE. DNA Repair (Amst) 85 102739 (2020)
  10. Functional Characterization of SMG7 Paralogs in Arabidopsis thaliana. Capitao C, Shukla N, Wandrolova A, Mittelsten Scheid O, Riha K. Front Plant Sci 9 1602 (2018)
  11. Swc4 positively regulates telomere length independently of its roles in NuA4 and SWR1 complexes. Liu JC, Li QJ, He MH, Hu C, Dai P, Meng FL, Zhou BO, Zhou JQ. Nucleic Acids Res 48 12792-12803 (2020)
  12. Cdc13 is predominant over Stn1 and Ten1 in preventing chromosome end fusions. Wu ZJ, Liu JC, Man X, Gu X, Li TY, Cai C, He MH, Shao Y, Lu N, Xue X, Qin Z, Zhou JQ. Elife 9 e53144 (2020)
  13. Refining the domain architecture model of the replication origin firing factor Treslin/TICRR. Ferreira P, Sanchez-Pulido L, Marko A, Ponting CP, Boos D. Life Sci Alliance 5 e202101088 (2022)
  14. The Sir4 H-BRCT domain interacts with phospho-proteins to sequester and repress yeast heterochromatin. Deshpande I, Keusch JJ, Challa K, Iesmantavicius V, Gasser SM, Gut H. EMBO J 38 e101744 (2019)
  15. Discovery and Evolution of New Domains in Yeast Heterochromatin Factor Sir4 and Its Partner Esc1. Faure G, Jézéquel K, Roisné-Hamelin F, Bitard-Feildel T, Lamiable A, Marcand S, Callebaut I. Genome Biol Evol 11 572-585 (2019)
  16. Loss of Ku's DNA end binding activity affects telomere length via destabilizing telomere-bound Est1 rather than altering TLC1 homeostasis. Lemon LD, Morris DK, Bertuch AA. Sci Rep 9 10607 (2019)
  17. Sir4 Deficiency Reverses Cell Senescence by Sub-Telomere Recombination. Liu J, Hong X, Wang L, Liang CY, Liu JP. Cells 10 778 (2021)
  18. Genome stability is guarded by yeast Rtt105 through multiple mechanisms. Corda Y, Maestroni L, Luciano P, Najem MY, Géli V. Genetics 217 iyaa035 (2021)
  19. Insights into the structure and function of Est3 from the Hansenula polymorpha telomerase. Shepelev NM, Mariasina SS, Mantsyzov AB, Malyavko AN, Efimov SV, Petrova OA, Rodina EV, Zvereva MI, Dontsova OA, Polshakov VI. Sci Rep 10 11109 (2020)
  20. Mapping mitonuclear epistasis using a novel recombinant yeast population. Nguyen THM, Tinz-Burdick A, Lenhardt M, Geertz M, Ramirez F, Schwartz M, Toledano M, Bonney B, Gaebler B, Liu W, Wolters JF, Chiu K, Fiumera AC, Fiumera HL. PLoS Genet 19 e1010401 (2023)
  21. Sir3 heterochromatin protein promotes non-homologous end joining by direct inhibition of Sae2. Bordelet H, Costa R, Brocas C, Dépagne J, Veaute X, Busso D, Batté A, Guérois R, Marcand S, Dubrana K. EMBO J 41 e108813 (2022)
  22. Telomerase subunit Est2 marks internal sites that are prone to accumulate DNA damage. Pandey S, Hajikazemi M, Zacheja T, Schalbetter S, Neale MJ, Baxter J, Guryev V, Hofmann A, Heermann DW, Juranek SA, Paeschke K. BMC Biol 19 247 (2021)
  23. 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, Shi S, Zeng Z, Wu J, Lei M. PLoS Genet 18 e1010308 (2022)
  24. Unraveling the stepwise maturation of the yeast telomerase including a Cse1 and Mtr10 mediated quality control checkpoint. Hirsch AG, Becker D, Lamping JP, Krebber H. Sci Rep 11 22174 (2021)
  25. Suppression of cdc13-2-associated senescence by pif1-m2 requires Ku-mediated telomerase recruitment. Fekete-Szücs E, Rosas Bringas FR, Stinus S, Chang M. G3 (Bethesda) 12 jkab360 (2022)
  26. Telomere length regulation by Rif1 protein from Hansenula polymorpha. Malyavko AN, Petrova OA, Zvereva MI, Polshakov VI, Dontsova OA. Elife 11 e75010 (2022)
  27. The Telomeric Cdc13 Protein from Yeast Hansenula polymorpha. Malyavko AN, Dontsova OA. Acta Naturae 12 84-88 (2020)
  28. A comprehensive map of hotspots of de novo telomere addition in Saccharomyces cerevisiae. Ngo K, Gittens TH, Gonzalez DI, Hatmaker EA, Plotkin S, Engle M, Friedman GA, Goldin M, Hoerr RE, Eichman BF, Rokas A, Benton ML, Friedman KL. Genetics 224 iyad076 (2023)
  29. Binding and structural studies of the complexes of type 1 ribosome inactivating protein from Momordica balsamina with uracil and uridine. Pandey SN, Iqbal N, Singh PK, Rastogi N, Kaur P, Sharma S, Singh TP. Proteins 87 99-109 (2019)
  30. Control of telomere length in yeast by SUMOylated PCNA and the Elg1 PCNA unloader. Singh P, Gazy I, Kupiec M. Elife 12 RP86990 (2023)
  31. Deletion of MEC1 suppresses the replicative senescence of the cdc13-2 mutant in Saccharomyces cerevisiae. Yao Y, Fekete-Szücs E, Rosas Bringas FR, Chang M. G3 (Bethesda) 13 jkad065 (2023)


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