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TERRA increases at short telomeres in yeast survivors and regulates survivor associated senescence (SAS)
Cancer cells achieve immortality by employing either homology-directed repair (HDR) or the telomerase enzyme to maintain telomeres. ALT (alternative lengthening of telomeres) refers to the subset of cancer cells that employ HDR. Many ALT features are conserved from yeast to human cells, with the yea...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9825167/ https://www.ncbi.nlm.nih.gov/pubmed/36513120 http://dx.doi.org/10.1093/nar/gkac1125 |
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author | Misino, Stefano Busch, Anke Wagner, Carolin B Bento, Fabio Luke, Brian |
author_facet | Misino, Stefano Busch, Anke Wagner, Carolin B Bento, Fabio Luke, Brian |
author_sort | Misino, Stefano |
collection | PubMed |
description | Cancer cells achieve immortality by employing either homology-directed repair (HDR) or the telomerase enzyme to maintain telomeres. ALT (alternative lengthening of telomeres) refers to the subset of cancer cells that employ HDR. Many ALT features are conserved from yeast to human cells, with the yeast equivalent being referred to as survivors. The non-coding RNA TERRA, and its ability to form RNA–DNA hybrids, has been implicated in ALT/survivor maintenance by promoting HDR. It is not understood which telomeres in ALT/survivors engage in HDR, nor is it clear which telomeres upregulate TERRA. Using yeast survivors as a model for ALT, we demonstrate that HDR only occurs at telomeres when they become critically short. Moreover, TERRA levels steadily increase as telomeres shorten and decrease again following HDR-mediated recombination. We observe that survivors undergo cycles of senescence, in a similar manner to non-survivors following telomerase loss, which we refer to as survivor associated senescence (SAS). Similar to ‘normal’ senescence, we report that RNA–DNA hybrids slow the rate of SAS, likely through the elongation of critically short telomeres, however decreasing the rate of telomere shortening may contribute to this effect. In summary, TERRA RNA–DNA hybrids regulate telomere dysfunction-induced senescence before and after survivor formation. |
format | Online Article Text |
id | pubmed-9825167 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-98251672023-01-09 TERRA increases at short telomeres in yeast survivors and regulates survivor associated senescence (SAS) Misino, Stefano Busch, Anke Wagner, Carolin B Bento, Fabio Luke, Brian Nucleic Acids Res Genome Integrity, Repair and Replication Cancer cells achieve immortality by employing either homology-directed repair (HDR) or the telomerase enzyme to maintain telomeres. ALT (alternative lengthening of telomeres) refers to the subset of cancer cells that employ HDR. Many ALT features are conserved from yeast to human cells, with the yeast equivalent being referred to as survivors. The non-coding RNA TERRA, and its ability to form RNA–DNA hybrids, has been implicated in ALT/survivor maintenance by promoting HDR. It is not understood which telomeres in ALT/survivors engage in HDR, nor is it clear which telomeres upregulate TERRA. Using yeast survivors as a model for ALT, we demonstrate that HDR only occurs at telomeres when they become critically short. Moreover, TERRA levels steadily increase as telomeres shorten and decrease again following HDR-mediated recombination. We observe that survivors undergo cycles of senescence, in a similar manner to non-survivors following telomerase loss, which we refer to as survivor associated senescence (SAS). Similar to ‘normal’ senescence, we report that RNA–DNA hybrids slow the rate of SAS, likely through the elongation of critically short telomeres, however decreasing the rate of telomere shortening may contribute to this effect. In summary, TERRA RNA–DNA hybrids regulate telomere dysfunction-induced senescence before and after survivor formation. Oxford University Press 2022-12-14 /pmc/articles/PMC9825167/ /pubmed/36513120 http://dx.doi.org/10.1093/nar/gkac1125 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Genome Integrity, Repair and Replication Misino, Stefano Busch, Anke Wagner, Carolin B Bento, Fabio Luke, Brian TERRA increases at short telomeres in yeast survivors and regulates survivor associated senescence (SAS) |
title | TERRA increases at short telomeres in yeast survivors and regulates survivor associated senescence (SAS) |
title_full | TERRA increases at short telomeres in yeast survivors and regulates survivor associated senescence (SAS) |
title_fullStr | TERRA increases at short telomeres in yeast survivors and regulates survivor associated senescence (SAS) |
title_full_unstemmed | TERRA increases at short telomeres in yeast survivors and regulates survivor associated senescence (SAS) |
title_short | TERRA increases at short telomeres in yeast survivors and regulates survivor associated senescence (SAS) |
title_sort | terra increases at short telomeres in yeast survivors and regulates survivor associated senescence (sas) |
topic | Genome Integrity, Repair and Replication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9825167/ https://www.ncbi.nlm.nih.gov/pubmed/36513120 http://dx.doi.org/10.1093/nar/gkac1125 |
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