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Structure of the human telomeric Stn1-Ten1 capping complex.

Bryan C, Rice C, Harkisheimer M, Schultz DC, Skordalakes E
PLoS One 8 e66756 (2013)
Cited: 58 times
EuropePMC logo PMID: 23826127

Abstract

The identification of the human homologue of the yeast CST in 2009 posed a new challenge in our understanding of the mechanism of telomere capping in higher eukaryotes. The high-resolution structure of the human Stn1-Ten1 (hStn1-Ten1) complex presented here reveals that hStn1 consists of an OB domain and tandem C-terminal wHTH motifs, while hTen1 consists of a single OB fold. Contacts between the OB domains facilitate formation of a complex that is strikingly similar to the replication protein A (RPA) and yeast Stn1-Ten1 (Ten1) complexes. The hStn1-Ten1 complex exhibits non-specific single-stranded DNA activity that is primarily dependent on hStn1. Cells expressing hStn1 mutants defective for dimerization with hTen1 display elongated telomeres and telomere defects associated with telomere uncapping, suggesting that the telomeric function of hCST is hTen1 dependent. Taken together the data presented here show that the structure of the hStn1-Ten1 subcomplex is conserved across species. Cell based assays indicate that hTen1 is critical for the telomeric function of hCST, both in telomere protection and downregulation of telomerase function.

Reviews - 4jqf mentioned but not cited (3)

  1. Structure and function of the telomeric CST complex. Rice C, Skordalakes E. Comput Struct Biotechnol J 14 161-167 (2016)
  2. Progress in Human and Tetrahymena Telomerase Structure Determination. Chan H, Wang Y, Feigon J. Annu Rev Biophys 46 199-225 (2017)
  3. Structural Features of Nucleoprotein CST/Shelterin Complex Involved in the Telomere Maintenance and Its Association with Disease Mutations. Amir M, Khan P, Queen A, Dohare R, Alajmi MF, Hussain A, Islam A, Ahmad F, Hassan I. Cells 9 (2020)

Articles - 4jqf mentioned but not cited (4)

  1. Structure of the human telomeric Stn1-Ten1 capping complex. Bryan C, Rice C, Harkisheimer M, Schultz DC, Skordalakes E. PLoS ONE 8 e66756 (2013)
  2. The structure of human CST reveals a decameric assembly bound to telomeric DNA. Lim CJ, Barbour AT, Zaug AJ, Goodrich KJ, McKay AE, Wuttke DS, Cech TR. Science 368 1081-1085 (2020)
  3. The dipeptidyl peptidase IV inhibitors vildagliptin and K-579 inhibit a phospholipase C: a case of promiscuous scaffolds in proteins. Chakraborty S, Rendón-Ramírez A, Ásgeirsson B, Dutta M, Ghosh AS, Oda M, Venkatramani R, Rao BJ, Dandekar AM, Goñi FM. F1000Res 2 286 (2013)
  4. Structural Analysis and Conformational Dynamics of STN1 Gene Mutations Involved in Coat Plus Syndrome. Amir M, Mohammad T, Kumar V, Alajmi MF, Rehman MT, Hussain A, Alam P, Dohare R, Islam A, Ahmad F, Hassan MI. Front Mol Biosci 6 41 (2019)


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  1. Biology of telomeres: lessons from budding yeast. Kupiec M. FEMS Microbiol. Rev. 38 144-171 (2014)
  2. Structural biology of telomeres and telomerase. Smith EM, Pendlebury DF, Nandakumar J. Cell Mol Life Sci 77 61-79 (2020)
  3. Roles of OB-Fold Proteins in Replication Stress. Nguyen DD, Kim EY, Sang PB, Chai W. Front Cell Dev Biol 8 574466 (2020)
  4. DNA Replication Origins and Fork Progression at Mammalian Telomeres. Higa M, Fujita M, Yoshida K. Genes (Basel) 8 (2017)
  5. Multiple facets of TPP1 in telomere maintenance. Rajavel M, Mullins MR, Taylor DJ. Biochim. Biophys. Acta 1844 1550-1559 (2014)
  6. Emerging roles of CST in maintaining genome stability and human disease. Stewart JA, Wang Y, Ackerson SM, Schuck PL. Front Biosci (Landmark Ed) 23 1564-1586 (2018)
  7. CST in maintaining genome stability: Beyond telomeres. Lyu X, Sang PB, Chai W. DNA Repair (Amst) 102 103104 (2021)
  8. CST-Polα/Primase: the second telomere maintenance machine. Cai SW, de Lange T. Genes Dev 37 555-569 (2023)
  9. Regulation of Antigenic Variation by Trypanosoma brucei Telomere Proteins Depends on Their Unique DNA Binding Activities. Li B, Zhao Y. Pathogens 10 967 (2021)
  10. Telomere Length and Oxidative Stress and Its Relation with Metabolic Syndrome Components in the Aging. Gavia-García G, Rosado-Pérez J, Arista-Ugalde TL, Aguiñiga-Sánchez I, Santiago-Osorio E, Mendoza-Núñez VM. Biology (Basel) 10 253 (2021)
  11. The enigma of excessively long telomeres in cancer: lessons learned from rare human POT1 variants. Gong Y, Stock AJ, Liu Y. Curr Opin Genet Dev 60 48-55 (2020)
  12. At the Beginning of the End and in the Middle of the Beginning: Structure and Maintenance of Telomeric DNA Repeats and Interstitial Telomeric Sequences. Aksenova AY, Mirkin SM. Genes (Basel) 10 (2019)
  13. Back to the future: The intimate and evolving connection between telomere-related factors and genotoxic stress. Barbero Barcenilla B, Shippen DE. J. Biol. Chem. 294 14803-14813 (2019)
  14. Heterogeneous Nuclear Ribonucleoproteins Involved in the Functioning of Telomeres in Malignant Cells. Shishkin SS, Kovalev LI, Pashintseva NV, Kovaleva MA, Lisitskaya K. Int J Mol Sci 20 (2019)
  15. Shaping human telomeres: from shelterin and CST complexes to telomeric chromatin organization. Lim CJ, Cech TR. Nat Rev Mol Cell Biol (2021)
  16. Telomeres and Cancer. Fan HC, Chang FW, Tsai JD, Lin KM, Chen CM, Lin SZ, Liu CA, Harn HJ. Life (Basel) 11 1405 (2021)

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  1. Structure of Tetrahymena telomerase reveals previously unknown subunits, functions, and interactions. Jiang J, Chan H, Cash DD, Miracco EJ, Ogorzalek Loo RR, Upton HE, Cascio D, O'Brien Johnson R, Collins K, Loo JA, Zhou ZH, Feigon J. Science 350 aab4070 (2015)
  2. Human TEN1 maintains telomere integrity and functions in genome-wide replication restart. Kasbek C, Wang F, Price CM. J. Biol. Chem. 288 30139-30150 (2013)
  3. Regulating telomere length from the inside out: the replication fork model. Greider CW. Genes Dev. 30 1483-1491 (2016)
  4. Mutations in STN1 cause Coats plus syndrome and are associated with genomic and telomere defects. Simon AJ, Lev A, Zhang Y, Weiss B, Rylova A, Eyal E, Kol N, Barel O, Cesarkas K, Soudack M, Greenberg-Kushnir N, Rhodes M, Wiest DL, Schiby G, Barshack I, Katz S, Pras E, Poran H, Reznik-Wolf H, Ribakovsky E, Simon C, Hazou W, Sidi Y, Lahad A, Katzir H, Sagie S, Aqeilan HA, Glousker G, Amariglio N, Tzfati Y, Selig S, Rechavi G, Somech R. J. Exp. Med. 213 1429-1440 (2016)
  5. A POT1 mutation implicates defective telomere end fill-in and telomere truncations in Coats plus. Takai H, Jenkinson E, Kabir S, Babul-Hirji R, Najm-Tehrani N, Chitayat DA, Crow YJ, de Lange T. Genes Dev. 30 812-826 (2016)
  6. CTC1-mediated C-strand fill-in is an essential step in telomere length maintenance. Feng X, Hsu SJ, Kasbek C, Chaiken M, Price CM. Nucleic Acids Res. 45 4281-4293 (2017)
  7. Human CST abundance determines recovery from diverse forms of DNA damage and replication stress. Wang F, Stewart J, Price CM. Cell Cycle 13 3488-3498 (2014)
  8. Telomere Replication Stress Induced by POT1 Inactivation Accelerates Tumorigenesis. Pinzaru AM, Hom RA, Beal A, Phillips AF, Ni E, Cardozo T, Nair N, Choi J, Wuttke DS, Sfeir A, Denchi EL. Cell Rep 15 2170-2184 (2016)
  9. The Tetrahymena telomerase p75-p45-p19 subcomplex is a unique CST complex. Wan B, Tang T, Upton H, Shuai J, Zhou Y, Li S, Chen J, Brunzelle JS, Zeng Z, Collins K, Wu J, Lei M. Nat. Struct. Mol. Biol. 22 1023-1026 (2015)
  10. Human CST Facilitates Genome-wide RAD51 Recruitment to GC-Rich Repetitive Sequences in Response to Replication Stress. Chastain M, Zhou Q, Shiva O, Fadri-Moskwik M, Whitmore L, Jia P, Dai X, Huang C, Ye P, Chai W. Cell Rep 16 1300-1314 (2016)
  11. STN1 OB Fold Mutation Alters DNA Binding and Affects Selective Aspects of CST Function. Bhattacharjee A, Stewart J, Chaiken M, Price CM. PLoS Genet. 12 e1006342 (2016)
  12. Regulation of human telomerase splicing by RNA:RNA pairing. Wong MS, Shay JW, Wright WE. Nat Commun 5 3306 (2014)
  13. Role of STN1 and DNA polymerase α in telomere stability and genome-wide replication in Arabidopsis. Derboven E, Ekker H, Kusenda B, Bulankova P, Riha K. PLoS Genet. 10 e1004682 (2014)
  14. Tying up the Ends: Plasticity in the Recognition of Single-Stranded DNA at Telomeres. Lloyd NR, Dickey TH, Hom RA, Wuttke DS. Biochemistry 55 5326-5340 (2016)
  15. Dynamic DNA binding, junction recognition and G4 melting activity underlie the telomeric and genome-wide roles of human CST. Bhattacharjee A, Wang Y, Diao J, Price CM. Nucleic Acids Res. 45 12311-12324 (2017)
  16. STN1-POLA2 interaction provides a basis for primase-pol α stimulation by human STN1. Ganduri S, Lue NF. Nucleic Acids Res. 45 9455-9466 (2017)
  17. Human CST Prefers G-Rich but Not Necessarily Telomeric Sequences. Hom RA, Wuttke DS. Biochemistry 56 4210-4218 (2017)
  18. Pol α-primase dependent nuclear localization of the mammalian CST complex. Kelich JM, Papaioannou H, Skordalakes E. Commun Biol 4 349 (2021)
  19. CTC1-STN1 terminates telomerase while STN1-TEN1 enables C-strand synthesis during telomere replication in colon cancer cells. Feng X, Hsu SJ, Bhattacharjee A, Wang Y, Diao J, Price CM. Nat Commun 9 2827 (2018)
  20. Chromosome segregation and organization are targets of 5'-Fluorouracil in eukaryotic cells. Mojardín L, Botet J, Moreno S, Salas M. Cell Cycle 14 206-218 (2015)
  21. The Telomere Binding Protein Cdc13 and the Single-Stranded DNA Binding Protein RPA Protect Telomeric DNA from Resection by Exonucleases. Greetham M, Skordalakes E, Lydall D, Connolly BA. J. Mol. Biol. 427 3023-3030 (2015)
  22. Dynamic Interactions of Arabidopsis TEN1: Stabilizing Telomeres in Response to Heat Stress. Lee JR, Xie X, Yang K, Zhang J, Lee SY, Shippen DE. Plant Cell 28 2212-2224 (2016)
  23. Hypothesis: Paralog Formation from Progenitor Proteins and Paralog Mutagenesis Spur the Rapid Evolution of Telomere Binding Proteins. Lustig AJ. Front Genet 7 10 (2016)
  24. Pathogenic CTC1 mutations cause global genome instabilities under replication stress. Wang Y, Chai W. Nucleic Acids Res. 46 3981-3992 (2018)
  25. Structural and functional analysis of an OB-fold in human Ctc1 implicated in telomere maintenance and bone marrow syndromes. Shastrula PK, Rice CT, Wang Z, Lieberman PM, Skordalakes E. Nucleic Acids Res. 46 972-984 (2018)
  26. Structure of Tetrahymena telomerase-bound CST with polymerase α-primase. He Y, Song H, Chan H, Liu B, Wang Y, Sušac L, Zhou ZH, Feigon J. Nature 608 813-818 (2022)
  27. Dynamic peptides of human TPP1 fulfill diverse functions in telomere maintenance. Rajavel M, Orban T, Xu M, Hernandez-Sanchez W, de la Fuente M, Palczewski K, Taylor DJ. Nucleic Acids Res. 44 10467-10479 (2016)
  28. Beyond Telomerase: Telomere Instability as a Novel Target for Cancer Therapy. Fadri-Moskwik M, Zhou Q, Chai W. J Mol Genet Med 7 (2013)
  29. CST does not evict elongating telomerase but prevents initiation by ssDNA binding. Zaug AJ, Lim CJ, Olson CL, Carilli MT, Goodrich KJ, Wuttke DS, Cech TR. Nucleic Acids Res 49 11653-11665 (2021)
  30. Crystallographic Studies of Telomerase. Hoffman H, Skordalakes E. Meth. Enzymol. 573 403-419 (2016)
  31. Human CST complex protects stalled replication forks by directly blocking MRE11 degradation of nascent-strand DNA. Lyu X, Lei KH, Biak Sang P, Shiva O, Chastain M, Chi P, Chai W. EMBO J 40 e103654 (2021)
  32. Human CTC1 promotes TopBP1 stability and CHK1 phosphorylation in response to telomere dysfunction and global replication stress. Ackerson SM, Gable CI, Stewart JA. Cell Cycle 19 3491-3507 (2020)
  33. Molecular architecture and oligomerization of Candida glabrata Cdc13 underpin its telomeric DNA-binding and unfolding activity. Coloma J, Gonzalez-Rodriguez N, Balaguer FA, Gmurczyk K, Aicart-Ramos C, Nuero ÓM, Luque-Ortega JR, Calugaru K, Lue NF, Moreno-Herrero F, Llorca O. Nucleic Acids Res 51 668-686 (2023)
  34. Structural and functional impact of non-synonymous SNPs in the CST complex subunit TEN1: structural genomics approach. Amir M, Kumar V, Mohammad T, Dohare R, Rehman MT, Alajmi MF, Hussain A, Ahmad F, Hassan MI. Biosci. Rep. 39 (2019)
  35. The Intrinsically Disordered Region in the Human STN1 OB-Fold Domain Is Important for Protecting Genome Stability. Chai W, Chastain M, Shiva O, Wang Y. Biology (Basel) 10 977 (2021)


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