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Tieing together loose ends: telomere instability in cancer and aging

Telomere maintenance is essential for maintaining genome integrity in both normal and cancer cells. Without functional telomeres, chromosomes lose their protective structure and undergo fusion and breakage events that drive further genome instability, including cell arrest or death. One means by whi...

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Detalles Bibliográficos
Autores principales: Borges, Gustavo, Criqui, Mélanie, Harrington, Lea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9490142/
https://www.ncbi.nlm.nih.gov/pubmed/35920280
http://dx.doi.org/10.1002/1878-0261.13299
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author Borges, Gustavo
Criqui, Mélanie
Harrington, Lea
author_facet Borges, Gustavo
Criqui, Mélanie
Harrington, Lea
author_sort Borges, Gustavo
collection PubMed
description Telomere maintenance is essential for maintaining genome integrity in both normal and cancer cells. Without functional telomeres, chromosomes lose their protective structure and undergo fusion and breakage events that drive further genome instability, including cell arrest or death. One means by which this loss can be overcome in stem cells and cancer cells is via re‐addition of G‐rich telomeric repeats by the telomerase reverse transcriptase (TERT). During aging of somatic tissues, however, insufficient telomerase expression leads to a proliferative arrest called replicative senescence, which is triggered when telomeres reach a critically short threshold that induces a DNA damage response. Cancer cells express telomerase but do not entirely escape telomere instability as they often possess short telomeres; hence there is often selection for genetic alterations in the TERT promoter that result in increased telomerase expression. In this review, we discuss our current understanding of the consequences of telomere instability in cancer and aging, and outline the opportunities and challenges that lie ahead in exploiting the reliance of cells on telomere maintenance for preserving genome stability.
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spelling pubmed-94901422022-09-30 Tieing together loose ends: telomere instability in cancer and aging Borges, Gustavo Criqui, Mélanie Harrington, Lea Mol Oncol Reviews Telomere maintenance is essential for maintaining genome integrity in both normal and cancer cells. Without functional telomeres, chromosomes lose their protective structure and undergo fusion and breakage events that drive further genome instability, including cell arrest or death. One means by which this loss can be overcome in stem cells and cancer cells is via re‐addition of G‐rich telomeric repeats by the telomerase reverse transcriptase (TERT). During aging of somatic tissues, however, insufficient telomerase expression leads to a proliferative arrest called replicative senescence, which is triggered when telomeres reach a critically short threshold that induces a DNA damage response. Cancer cells express telomerase but do not entirely escape telomere instability as they often possess short telomeres; hence there is often selection for genetic alterations in the TERT promoter that result in increased telomerase expression. In this review, we discuss our current understanding of the consequences of telomere instability in cancer and aging, and outline the opportunities and challenges that lie ahead in exploiting the reliance of cells on telomere maintenance for preserving genome stability. John Wiley and Sons Inc. 2022-08-16 2022-09 /pmc/articles/PMC9490142/ /pubmed/35920280 http://dx.doi.org/10.1002/1878-0261.13299 Text en © 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Reviews
Borges, Gustavo
Criqui, Mélanie
Harrington, Lea
Tieing together loose ends: telomere instability in cancer and aging
title Tieing together loose ends: telomere instability in cancer and aging
title_full Tieing together loose ends: telomere instability in cancer and aging
title_fullStr Tieing together loose ends: telomere instability in cancer and aging
title_full_unstemmed Tieing together loose ends: telomere instability in cancer and aging
title_short Tieing together loose ends: telomere instability in cancer and aging
title_sort tieing together loose ends: telomere instability in cancer and aging
topic Reviews
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9490142/
https://www.ncbi.nlm.nih.gov/pubmed/35920280
http://dx.doi.org/10.1002/1878-0261.13299
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