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Impaired cohesion and homologous recombination during replicative aging in budding yeast
The causal relationship between genomic instability and replicative aging is unclear. We reveal here that genomic instability at the budding yeast ribosomal DNA (rDNA) locus increases during aging, potentially due to the reduced cohesion that we uncovered during aging caused by the reduced abundance...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5810620/ https://www.ncbi.nlm.nih.gov/pubmed/29441364 http://dx.doi.org/10.1126/sciadv.aaq0236 |
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author | Pal, Sangita Postnikoff, Spike D. Chavez, Myrriah Tyler, Jessica K. |
author_facet | Pal, Sangita Postnikoff, Spike D. Chavez, Myrriah Tyler, Jessica K. |
author_sort | Pal, Sangita |
collection | PubMed |
description | The causal relationship between genomic instability and replicative aging is unclear. We reveal here that genomic instability at the budding yeast ribosomal DNA (rDNA) locus increases during aging, potentially due to the reduced cohesion that we uncovered during aging caused by the reduced abundance of multiple cohesin subunits, promoting increased global chromosomal instability. In agreement, cohesion is lost during aging at other chromosomal locations in addition to the rDNA, including centromeres. The genomic instability in old cells is exacerbated by a defect in DNA double-strand break (DSB) repair that we uncovered in old yeast. This was due to limiting levels of key homologous recombination proteins because overexpression of Rad51 or Mre11 reduced the accumulation of DSBs and largely restored DSB repair in old cells. We propose that increased rDNA instability and the reduced DSB repair capacity of old cells contribute to the progressive accumulation of global chromosomal DNA breaks, where exceeding a threshold of genomic DNA damage ends the replicative life span. |
format | Online Article Text |
id | pubmed-5810620 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-58106202018-02-13 Impaired cohesion and homologous recombination during replicative aging in budding yeast Pal, Sangita Postnikoff, Spike D. Chavez, Myrriah Tyler, Jessica K. Sci Adv Research Articles The causal relationship between genomic instability and replicative aging is unclear. We reveal here that genomic instability at the budding yeast ribosomal DNA (rDNA) locus increases during aging, potentially due to the reduced cohesion that we uncovered during aging caused by the reduced abundance of multiple cohesin subunits, promoting increased global chromosomal instability. In agreement, cohesion is lost during aging at other chromosomal locations in addition to the rDNA, including centromeres. The genomic instability in old cells is exacerbated by a defect in DNA double-strand break (DSB) repair that we uncovered in old yeast. This was due to limiting levels of key homologous recombination proteins because overexpression of Rad51 or Mre11 reduced the accumulation of DSBs and largely restored DSB repair in old cells. We propose that increased rDNA instability and the reduced DSB repair capacity of old cells contribute to the progressive accumulation of global chromosomal DNA breaks, where exceeding a threshold of genomic DNA damage ends the replicative life span. American Association for the Advancement of Science 2018-02-07 /pmc/articles/PMC5810620/ /pubmed/29441364 http://dx.doi.org/10.1126/sciadv.aaq0236 Text en Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles Pal, Sangita Postnikoff, Spike D. Chavez, Myrriah Tyler, Jessica K. Impaired cohesion and homologous recombination during replicative aging in budding yeast |
title | Impaired cohesion and homologous recombination during replicative aging in budding yeast |
title_full | Impaired cohesion and homologous recombination during replicative aging in budding yeast |
title_fullStr | Impaired cohesion and homologous recombination during replicative aging in budding yeast |
title_full_unstemmed | Impaired cohesion and homologous recombination during replicative aging in budding yeast |
title_short | Impaired cohesion and homologous recombination during replicative aging in budding yeast |
title_sort | impaired cohesion and homologous recombination during replicative aging in budding yeast |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5810620/ https://www.ncbi.nlm.nih.gov/pubmed/29441364 http://dx.doi.org/10.1126/sciadv.aaq0236 |
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