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Senescence in yeast is associated with amplified linear fragments of chromosome XII rather than ribosomal DNA circle accumulation
The massive accumulation of extrachromosomal ribosomal DNA circles (ERCs) in yeast mother cells has been long cited as the primary driver of replicative ageing. ERCs arise through ribosomal DNA (rDNA) recombination, and a wealth of genetic data connects rDNA instability events giving rise to ERCs wi...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10464983/ https://www.ncbi.nlm.nih.gov/pubmed/37643194 http://dx.doi.org/10.1371/journal.pbio.3002250 |
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author | Zylstra, Andre Hadj-Moussa, Hanane Horkai, Dorottya Whale, Alex J. Piguet, Baptiste Houseley, Jonathan |
author_facet | Zylstra, Andre Hadj-Moussa, Hanane Horkai, Dorottya Whale, Alex J. Piguet, Baptiste Houseley, Jonathan |
author_sort | Zylstra, Andre |
collection | PubMed |
description | The massive accumulation of extrachromosomal ribosomal DNA circles (ERCs) in yeast mother cells has been long cited as the primary driver of replicative ageing. ERCs arise through ribosomal DNA (rDNA) recombination, and a wealth of genetic data connects rDNA instability events giving rise to ERCs with shortened life span and other ageing pathologies. However, we understand little about the molecular effects of ERC accumulation. Here, we studied ageing in the presence and absence of ERCs, and unexpectedly found no evidence of gene expression differences that might indicate stress responses or metabolic feedback caused by ERCs. Neither did we observe any global change in the widespread disruption of gene expression that accompanies yeast ageing, altogether suggesting that ERCs are largely inert. Much of the differential gene expression that accompanies ageing in yeast was actually associated with markers of the senescence entry point (SEP), showing that senescence, rather than age, underlies these changes. Cells passed the SEP irrespective of ERCs, but we found the SEP to be associated with copy number amplification of a region of chromosome XII between the rDNA and the telomere (ChrXIIr) forming linear fragments up to approximately 1.8 Mb size, which arise in aged cells due to rDNA instability but through a different mechanism to ERCs. Therefore, although rDNA copy number increases dramatically with age due to ERC accumulation, our findings implicate ChrXIIr, rather than ERCs, as the primary driver of senescence during budding yeast ageing. |
format | Online Article Text |
id | pubmed-10464983 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-104649832023-08-30 Senescence in yeast is associated with amplified linear fragments of chromosome XII rather than ribosomal DNA circle accumulation Zylstra, Andre Hadj-Moussa, Hanane Horkai, Dorottya Whale, Alex J. Piguet, Baptiste Houseley, Jonathan PLoS Biol Research Article The massive accumulation of extrachromosomal ribosomal DNA circles (ERCs) in yeast mother cells has been long cited as the primary driver of replicative ageing. ERCs arise through ribosomal DNA (rDNA) recombination, and a wealth of genetic data connects rDNA instability events giving rise to ERCs with shortened life span and other ageing pathologies. However, we understand little about the molecular effects of ERC accumulation. Here, we studied ageing in the presence and absence of ERCs, and unexpectedly found no evidence of gene expression differences that might indicate stress responses or metabolic feedback caused by ERCs. Neither did we observe any global change in the widespread disruption of gene expression that accompanies yeast ageing, altogether suggesting that ERCs are largely inert. Much of the differential gene expression that accompanies ageing in yeast was actually associated with markers of the senescence entry point (SEP), showing that senescence, rather than age, underlies these changes. Cells passed the SEP irrespective of ERCs, but we found the SEP to be associated with copy number amplification of a region of chromosome XII between the rDNA and the telomere (ChrXIIr) forming linear fragments up to approximately 1.8 Mb size, which arise in aged cells due to rDNA instability but through a different mechanism to ERCs. Therefore, although rDNA copy number increases dramatically with age due to ERC accumulation, our findings implicate ChrXIIr, rather than ERCs, as the primary driver of senescence during budding yeast ageing. Public Library of Science 2023-08-29 /pmc/articles/PMC10464983/ /pubmed/37643194 http://dx.doi.org/10.1371/journal.pbio.3002250 Text en © 2023 Zylstra et al 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 use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Zylstra, Andre Hadj-Moussa, Hanane Horkai, Dorottya Whale, Alex J. Piguet, Baptiste Houseley, Jonathan Senescence in yeast is associated with amplified linear fragments of chromosome XII rather than ribosomal DNA circle accumulation |
title | Senescence in yeast is associated with amplified linear fragments of chromosome XII rather than ribosomal DNA circle accumulation |
title_full | Senescence in yeast is associated with amplified linear fragments of chromosome XII rather than ribosomal DNA circle accumulation |
title_fullStr | Senescence in yeast is associated with amplified linear fragments of chromosome XII rather than ribosomal DNA circle accumulation |
title_full_unstemmed | Senescence in yeast is associated with amplified linear fragments of chromosome XII rather than ribosomal DNA circle accumulation |
title_short | Senescence in yeast is associated with amplified linear fragments of chromosome XII rather than ribosomal DNA circle accumulation |
title_sort | senescence in yeast is associated with amplified linear fragments of chromosome xii rather than ribosomal dna circle accumulation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10464983/ https://www.ncbi.nlm.nih.gov/pubmed/37643194 http://dx.doi.org/10.1371/journal.pbio.3002250 |
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