7uy8 › Citations

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 (2022)
Related entries: 7uy5, 7uy6, 7uy7

Cited: 16 times
EuropePMC logo PMID: 35831498

Abstract

Telomeres are the physical ends of linear chromosomes. They are composed of short repeating sequences (such as TTGGGG in the G-strand for Tetrahymena thermophila) of double-stranded DNA with a single-strand 3' overhang of the G-strand and, in humans, the six shelterin proteins: TPP1, POT1, TRF1, TRF2, RAP1 and TIN21,2. TPP1 and POT1 associate with the 3' overhang, with POT1 binding the G-strand3 and TPP1 (in complex with TIN24) recruiting telomerase via interaction with telomerase reverse transcriptase5 (TERT). The telomere DNA ends are replicated and maintained by telomerase6, for the G-strand, and subsequently DNA polymerase α-primase7,8 (PolαPrim), for the C-strand9. PolαPrim activity is stimulated by the heterotrimeric complex CTC1-STN1-TEN110-12 (CST), but the structural basis of the recruitment of PolαPrim and CST to telomere ends remains unknown. Here we report cryo-electron microscopy (cryo-EM) structures of Tetrahymena CST in the context of the telomerase holoenzyme, in both the absence and the presence of PolαPrim, and of PolαPrim alone. Tetrahymena Ctc1 binds telomerase subunit p50, a TPP1 orthologue, on a flexible Ctc1 binding motif revealed by cryo-EM and NMR spectroscopy. The PolαPrim polymerase subunit POLA1 binds Ctc1 and Stn1, and its interface with Ctc1 forms an entry port for G-strand DNA to the POLA1 active site. We thus provide a snapshot of four key components that are required for telomeric DNA synthesis in a single active complex-telomerase-core ribonucleoprotein, p50, CST and PolαPrim-that provides insights into the recruitment of CST and PolαPrim and the handoff between G-strand and C-strand synthesis.

Articles - 7uy8 mentioned but not cited (1)

  1. research-article Flexibility and distributive synthesis regulate RNA priming and handoff in human DNA polymerase α-primase. Cordoba JJ, Mullins EA, Salay LE, Eichman BF, Chazin WJ. bioRxiv 2023.08.01.551538 (2023)


Reviews citing this publication (7)

  1. CST-Polα/Primase: the second telomere maintenance machine. Cai SW, de Lange T. Genes Dev 37 555-569 (2023)
  2. 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)
  3. 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)
  4. Models for human telomere C-strand fill-in by CST-Polα-primase. He Q, Lim CJ. Trends Biochem Sci 48 860-872 (2023)
  5. Orchestrating nucleic acid-protein interactions at chromosome ends: telomerase mechanisms come into focus. Lue NF, Autexier C. Nat Struct Mol Biol 30 878-890 (2023)
  6. Telomeres and Their Neighbors. Jenner LP, Peska V, Fulnečková J, Sýkorová E. Genes (Basel) 13 1663 (2022)
  7. Replication Protein A, the Main Eukaryotic Single-Stranded DNA Binding Protein, a Focal Point in Cellular DNA Metabolism. Nasheuer HP, Meaney AM, Hulshoff T, Thiele I, Onwubiko NO. Int J Mol Sci 25 588 (2024)

Articles citing this publication (8)

  1. 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)
  2. Reconstitution of a telomeric replicon organized by CST. Zaug AJ, Goodrich KJ, Song JJ, Sullivan AE, Cech TR. Nature 608 819-825 (2022)
  3. How Pol α-primase is targeted to replisomes to prime eukaryotic DNA replication. Jones ML, Aria V, Baris Y, Yeeles JTP. Mol Cell 83 2911-2924.e16 (2023)
  4. Deciphering RNA G-quadruplex function during the early steps of HIV-1 infection. Amrane S, Jaubert C, Bedrat A, Rundstadler T, Recordon-Pinson P, Aknin C, Guédin A, De Rache A, Bartolucci L, Diene I, Lemoine F, Gascuel O, Pratviel G, Mergny JL, Andreola ML. Nucleic Acids Res 50 12328-12343 (2022)
  5. Molecular choreography of primer synthesis by the eukaryotic Pol α-primase. Yuan Z, Georgescu R, Li H, O'Donnell ME. Nat Commun 14 3697 (2023)
  6. A novel mutation of CTC1 leads to telomere shortening in a chinese family with interstitial lung disease. Liu L, Luo H, Sheng Y, Kang X, Peng H, Luo H, Fan LL. Hereditas 160 37 (2023)
  7. CryoEM reveals oligomeric isomers of a multienzyme complex and assembly mechanics. Lee JKJ, Liu YT, Hu JJ, Aphasizheva I, Aphasizhev R, Zhou ZH. J Struct Biol X 7 100088 (2023)
  8. Distinct RPA functions promote eukaryotic DNA replication initiation and elongation. Pike AM, Friend CM, Bell SP. Nucleic Acids Res 51 10506-10518 (2023)


Quick links