The end protection problem—an unexpected twist in the tail
Open accessAbstract
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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Mechanisms and Regulation of Cellular Senescence
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Telomeric 8-Oxoguanine Drives Rapid Premature Senescence In The Absence Of Telomere Shortening
Barnes, R. P., de Rosa, M., Thosar, S. A., Detwiler, A. C., Roginskaya, V., Van Houten, B., Bruchez, M. P., Stewart-Ornstein, J., & Opresko, P. L. (2021) · doi:10.1101/2021.05.05.442662
- Authors
- Ruis, P., & Boulton, S. J.
- Affiliations
- The Francis Crick Institute (GB)
- ORCID
- Boulton, Simon J.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2020-12-23
- Volume
- 35
- Issue
- 1-2
- Pages
- 1-21
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC7778267
- OpenAlex
- W3115175503
- Cited by
- 57
- References
- 177
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- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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