The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
Senescence Induced by Altered Telomere State, Not Telomere Loss
Abstract
Primary human cells in culture invariably stop dividing and enter a state of growth arrest called replicative senescence. This transition is induced by programmed telomere shortening, but the underlying mechanisms are unclear. Here, we report that overexpression of TRF2, a telomeric DNA binding protein, increased the rate of telomere shortening in primary cells without accelerating senescence. TRF2 reduced the senescence setpoint, defined as telomere length at senescence, from 7 to 4 kilobases. TRF2 protected critically short telomeres from fusion and repressed chromosome-end fusions in presenescent cultures, which explains the ability of TRF2 to delay senescence. Thus, replicative senescence is induced by a change in the protected status of shortened telomeres rather than by a complete loss of telomeric DNA.
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“In addition, the TRF2-dependent suppression of DNA repair within telomeres can yield DDR signaling from telomere-associated damage resulting from causes other than telomere shortening (Karlseder et al. 2002; Fumagalli et al. 2012).”
From Cellular senescence and its effector programs (2014) · cites this paper as Karlseder et al. 2002
In the citing paper
“Furthermore, over-expression of the shelterin subunit telomeric repeat-binding factor 2 (TRF2; also known as TERF2) can delay the onset of senescence44, arguing that the DDR in senescence is due to an insufficient loading of shelterin at the shortened telomeres.”
From Telomeres in cancer: tumour suppression and genome instability (2017) · cites this paper as [44]
In the citing paper
“In agreement, TRF2 overexpression delays replicative senescence onset [101], indicating that TRF2 capacity to sequester the telomere terminus via the t-loop conformation [88] might suppress the DNA damage signal from too short telomere ends and protect them from ATM signaling.”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [101]
Citations
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DNA Damage Foci at Dysfunctional Telomeres
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Metadata
- Authors
- Karlseder, J., Smogorzewska, A., & de Lange, T.
- Affiliations
- Rockefeller University (US)
- Laboratory for Cell Biology and Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
- Venue
- Science
- Published
- 2002-03-29
- Volume
- 295
- Issue
- 5564
- Pages
- 2446-2449
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2088926897
- Cited by
- 796
- References
- 25
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 22 · 2023: 11 · 2022: 14 · 2021: 22 · 2020: 18 · 2019: 19 · 2018: 26 · 2017: 22 · 2016: 20 · 2015: 29 · 2014: 24 · 2013: 22 · 2012: 35
- FWCI
- 47.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG 16643)
- National Cancer Institute (R01CA076027, CA76027)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- replicative senescence, telomere shortening, TRF2, telomere length, telomere fusion, primary human cells, growth arrest
- MeSH terms
- Antigens, Polyomavirus Transforming, Cell Division, Cell Line, Cells, Cultured, DNA, DNA-Binding Proteins, Humans, Oncogene Proteins, Viral, Repressor Proteins, Retroviridae, Transformation, Genetic, Tumor Suppressor Protein p53, Retinoblastoma Protein, Telomere, Cellular Senescence, Telomeric Repeat Binding Protein 2, Papillomavirus E7 Proteins
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