Cited by 57Telomeres, Telomerase, and SenescenceDNA Repair MechanismsGenomics and Chromatin Dynamics

The end protection problem—an unexpected twist in the tail

Open access
Ruis, Phil, Boulton, Simon J.·2021·Genes & Development

Abstract

In this perspective, we introduce shelterin and the mechanisms of ATM activation and NHEJ at telomeres, before discussing the following questions: How are t-loops proposed to protect chromosome ends and what is the evidence for this model? Can other models explain how TRF2 mediates end protection? Could t-loops be pathological structures? How is end protection achieved in pluripotent cells? What do the insights into telomere end protection in pluripotent cells mean for the t-loop model of end protection? Why might different cell states have evolved different mechanisms of end protection? Finally, we offer support for an updated t-loop model of end protection, suggesting that the data is supportive of a critical role for t-loops in protecting chromosome ends from NHEJ and ATM activation, but that other mechanisms are involved. Finally, we propose that t-loops are likely dynamic, rather than static, structures.

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  • Shelterin allows the efficient suppression of non-homologous end joining and ATM activation at chromosome ends.

    “Shelterin allows the efficient suppression of non-homologous end joining (NHEJ) and ATM activation at chromosome ends [89].”

    From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [89]

  • Telomeres shorten at each cell replication because of the end-replication problem and post replicative end-processing.

    “Telomeres shorten at each cell replication because of the end-replication problem and post replicative end-processing [89,90].”

    From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [89]

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Research works printed but not linked: 4

  1. Biessmann H, Mason JM. 1997 Telomere maintenance without telomerase. Chromosoma 106: 63– 69. 10.1007/s004120050225 9215555 · DOI
  2. Ding H, Schertzer M, Wu X, Gertsenstein M, Selig S, Kammori M, Pourvali R, Poon S, Vulto I, Chavez E, 2004 Regulation of murine telomere length by Rtel: an essential gene encoding a helicase-like protein. Cell 117: 873– 886. 10.1016/j.cell.2004.05.026 15210109 · DOI · Paper page
  3. Li B, Oestreich S, de Lange T. 2000 Identification of human Rap1: implications for telomere evolution. Cell 101: 471– 483. 10.1016/S0092-8674(00)80858-2 10850490 · DOI
  4. Sarek G, Vannier JB, Panier S, Petrini JHJ, Boulton SJ. 2015b TRF2 recruits RTEL1 to telomeres in S phase to promote t-loop unwinding. Mol Cell 57: 622– 635. 10.1016/j.molcel.2014.12.024 25620558 PMC4339303 · DOI

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Authors
Ruis, P., & Boulton, S. J.
Affiliations
The Francis Crick Institute (GB)
Venue
Genes & Development
Published
2020-12-23
Volume
35
Issue
1-2
Pages
1-21
ISSN
  • 0890-9369 (ISSN-L)
  • 1549-5477
OpenAlex
W3115175503
Cited by
57
References
177
Citations by year
2026: 4 · 2025: 14 · 2024: 13 · 2023: 8 · 2022: 8 · 2021: 10
Type
posted content
Language
en
Open access
Licence
cc-by
Locations
  • Genes & Development (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Figshare (submittedVersion, cc-by)
Funders
  • Francis Crick Institute
  • Cancer Research UK (FC0010048)
  • UK Medical Research Council (FC0010048)
  • Wellcome Trust (FC0010048)
  • European Research Council
Topics
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
telomere protection, shelterin, T-loop, TRF2, ATM activation, non-homologous end joining, telomeres, pluripotent cells, telomere length, telomere dynamics
MeSH terms
Animals, DNA Repair, Humans, Models, Biological, Telomere, Telomeric Repeat Binding Protein 2, Pluripotent Stem Cells, Chromosomal Instability, Embryonic Stem Cells, DNA Breaks, Double-Stranded, DNA End-Joining Repair, Ataxia Telangiectasia Mutated Proteins

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