6w6w › Citations

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)
Cited: 49 times
EuropePMC logo PMID: 32499435

Abstract

The CTC1-STN1-TEN1 (CST) complex is essential for telomere maintenance and resolution of stalled replication forks genome-wide. Here, we report the 3.0-angstrom cryo-electron microscopy structure of human CST bound to telomeric single-stranded DNA (ssDNA), which assembles as a decameric supercomplex. The atomic model of the 134-kilodalton CTC1 subunit, built almost entirely de novo, reveals the overall architecture of CST and the DNA-binding anchor site. The carboxyl-terminal domain of STN1 interacts with CTC1 at two separate docking sites, allowing allosteric mediation of CST decamer assembly. Furthermore, ssDNA appears to staple two monomers to nucleate decamer assembly. CTC1 has stronger structural similarity to Replication Protein A than the expected similarity to yeast Cdc13. The decameric structure suggests that CST can organize ssDNA analogously to the nucleosome's organization of double-stranded DNA.

Reviews - 6w6w mentioned but not cited (2)

  1. CST in maintaining genome stability: Beyond telomeres. Lyu X, Sang PB, Chai W. DNA Repair (Amst) 102 103104 (2021)
  2. Shaping human telomeres: from shelterin and CST complexes to telomeric chromatin organization. Lim CJ, Cech TR. Nat Rev Mol Cell Biol (2021)

Articles - 6w6w mentioned but not cited (7)

  1. 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)
  2. Structural genomics approach to investigate deleterious impact of nsSNPs in conserved telomere maintenance component 1. Choudhury A, Mohammad T, Samarth N, Hussain A, Rehman MT, Islam A, Alajmi MF, Singh S, Hassan MI. Sci Rep 11 10202 (2021)
  3. Cryo-EM structure of the human CST-Polα/primase complex in a recruitment state. Cai SW, Zinder JC, Svetlov V, Bush MW, Nudler E, Walz T, de Lange T. Nat Struct Mol Biol 29 813-819 (2022)
  4. Structures of the human CST-Polα-primase complex bound to telomere templates. He Q, Lin X, Chavez BL, Agrawal S, Lusk BL, Lim CJ. Nature 608 826-832 (2022)
  5. CST/Polα/primase-mediated fill-in synthesis at DSBs. Mirman Z, Cai S, de Lange T. Cell Cycle 22 379-389 (2023)
  6. Remote Homology Detection Identifies a Eukaryotic RPA DBD-C-like DNA Binding Domain as a Conserved Feature of Archaeal Rpa1-Like Proteins. MacNeill SA. Front Mol Biosci 8 675229 (2021)
  7. research-article Structural basis of CST-Polα/Primase recruitment and regulation by POT1 at telomeres. Cai SW, Takai H, Walz T, de Lange T. bioRxiv 2023.05.08.539880 (2023)


Reviews citing this publication (18)

  1. Roles of OB-Fold Proteins in Replication Stress. Nguyen DD, Kim EY, Sang PB, Chai W. Front Cell Dev Biol 8 574466 (2020)
  2. Molecular mechanisms of telomere biology disorders. Grill S, Nandakumar J. J Biol Chem 296 100064 (2021)
  3. G4-quadruplex-binding proteins: review and insights into selectivity. Meier-Stephenson V. Biophys Rev 14 635-654 (2022)
  4. Telomere Replication: Solving Multiple End Replication Problems. Bonnell E, Pasquier E, Wellinger RJ. Front Cell Dev Biol 9 668171 (2021)
  5. OB-Folds and Genome Maintenance: Targeting Protein-DNA Interactions for Cancer Therapy. Par S, Vaides S, VanderVere-Carozza PS, Pawelczak KS, Stewart J, Turchi JJ. Cancers (Basel) 13 3346 (2021)
  6. CST-Polα/Primase: the second telomere maintenance machine. Cai SW, de Lange T. Genes Dev 37 555-569 (2023)
  7. G-Quadruplex-Binding Proteins: Promising Targets for Drug Design. Shu H, Zhang R, Xiao K, Yang J, Sun X. Biomolecules 12 648 (2022)
  8. RPA-like single-stranded DNA-binding protein complexes including CST serve as specialized processivity factors for polymerases. Barbour AT, Wuttke DS. Curr Opin Struct Biol 81 102611 (2023)
  9. To Join or Not to Join: Decision Points Along the Pathway to Double-Strand Break Repair vs. Chromosome End Protection. Ackerson SM, Romney C, Schuck PL, Stewart JA. Front Cell Dev Biol 9 708763 (2021)
  10. Cold-Shock Domains-Abundance, Structure, Properties, and Nucleic-Acid Binding. Heinemann U, Roske Y. Cancers (Basel) 13 (2021)
  11. Immediate-Early, Early, and Late Responses to DNA Double Stranded Breaks. Kieffer SR, Lowndes NF. Front Genet 13 793884 (2022)
  12. Lagging Strand Initiation Processes in DNA Replication of Eukaryotes-Strings of Highly Coordinated Reactions Governed by Multiprotein Complexes. Nasheuer HP, Onwubiko NO. Genes (Basel) 14 1012 (2023)
  13. Looking at Biomolecular Interactions through the Lens of Correlated Fluorescence Microscopy and Optical Tweezers. Haghizadeh A, Iftikhar M, Dandpat SS, Simpson T. Int J Mol Sci 24 2668 (2023)
  14. Models for human telomere C-strand fill-in by CST-Polα-primase. He Q, Lim CJ. Trends Biochem Sci 48 860-872 (2023)
  15. OB-fold Families of Genome Guardians: A Universal Theme Constructed From the Small β-barrel Building Block. Bianco PR. Front Mol Biosci 9 784451 (2022)
  16. 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)
  17. Telomeres and Cancer. Fan HC, Chang FW, Tsai JD, Lin KM, Chen CM, Lin SZ, Liu CA, Harn HJ. Life (Basel) 11 1405 (2021)
  18. When the Ends Justify the Means: Regulation of Telomere Addition at Double-Strand Breaks in Yeast. Hoerr RE, Ngo K, Friedman KL. Front Cell Dev Biol 9 655377 (2021)

Articles citing this publication (22)

  1. Highly accurate protein structure prediction with AlphaFold. Jumper J, Evans R, Pritzel A, Green T, Figurnov M, Ronneberger O, Tunyasuvunakool K, Bates R, Žídek A, Potapenko A, Bridgland A, Meyer C, Kohl SAA, Ballard AJ, Cowie A, Romera-Paredes B, Nikolov S, Jain R, Adler J, Back T, Petersen S, Reiman D, Clancy E, Zielinski M, Steinegger M, Pacholska M, Berghammer T, Bodenstein S, Silver D, Vinyals O, Senior AW, Kavukcuoglu K, Kohli P, Hassabis D. Nature 596 583-589 (2021)
  2. Pol α-primase dependent nuclear localization of the mammalian CST complex. Kelich JM, Papaioannou H, Skordalakes E. Commun Biol 4 349 (2021)
  3. Small tandem DNA duplications result from CST-guided Pol α-primase action at DNA break termini. Schimmel J, Muñoz-Subirana N, Kool H, van Schendel R, Tijsterman M. Nat Commun 12 4843 (2021)
  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. Reconstitution of a telomeric replicon organized by CST. Zaug AJ, Goodrich KJ, Song JJ, Sullivan AE, Cech TR. Nature 608 819-825 (2022)
  6. 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)
  7. An AlphaFold2 map of the 53BP1 pathway identifies a direct SHLD3-RIF1 interaction critical for shieldin activity. Sifri C, Hoeg L, Durocher D, Setiaputra D. EMBO Rep 24 e56834 (2023)
  8. The evolution of metazoan shelterin. Myler LR, Kinzig CG, Sasi NK, Zakusilo G, Cai SW, de Lange T. Genes Dev 35 1625-1641 (2021)
  9. 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)
  10. CTC1 OB-B interaction with TPP1 terminates telomerase and prevents telomere overextension. Wang H, Ma T, Zhang X, Chen W, Lan Y, Kuang G, Hsu SJ, He Z, Chen Y, Stewart J, Bhattacharjee A, Luo Z, Price C, Feng X. Nucleic Acids Res 51 4914-4928 (2023)
  11. CaMKK2 and CHK1 phosphorylate human STN1 in response to replication stress to protect stalled forks from aberrant resection. Jaiswal RK, Lei KH, Chastain M, Wang Y, Shiva O, Li S, You Z, Chi P, Chai W. Nat Commun 14 7882 (2023)
  12. Control of telomere length in yeast by SUMOylated PCNA and the Elg1 PCNA unloader. Singh P, Gazy I, Kupiec M. Elife 12 RP86990 (2023)
  13. Crosstalk between CST and RPA regulates RAD51 activity during replication stress. Lei KH, Yang HL, Chang HY, Yeh HY, Nguyen DD, Lee TY, Lyu X, Chastain M, Chai W, Li HW, Chi P. Nat Commun 12 6412 (2021)
  14. DNA-binding mechanism and evolution of replication protein A. Madru C, Martínez-Carranza M, Laurent S, Alberti AC, Chevreuil M, Raynal B, Haouz A, Le Meur RA, Delarue M, Henneke G, Flament D, Krupovic M, Legrand P, Sauguet L. Nat Commun 14 2326 (2023)
  15. 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)
  16. 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)
  17. 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)
  18. RPA engages telomeric G-quadruplexes more effectively than CST. Olson CL, Barbour AT, Wieser TA, Wuttke DS. Nucleic Acids Res 51 5073-5086 (2023)
  19. Replication Protein A Utilizes Differential Engagement of Its DNA-Binding Domains to Bind Biologically Relevant ssDNAs in Diverse Binding Modes. Wieser TA, Wuttke DS. Biochemistry 61 2592-2606 (2022)
  20. The CST complex facilitates cell survival under oxidative genotoxic stress. Hara T, Nakaoka H, Miyoshi T, Ishikawa F. PLoS One 18 e0289304 (2023)
  21. 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)
  22. Ustilago maydis telomere protein Pot1 harbors an extra N-terminal OB fold and regulates homology-directed DNA repair factors in a dichotomous and context-dependent manner. Zahid S, Aloe S, Sutherland JH, Holloman WK, Lue NF. PLoS Genet 18 e1010182 (2022)


Quick links