Deregulation of the G1/S-phase transition is the proximal cause of mortality in old yeast mother cells

Budding yeast cells produce a finite number of daughter cells before they die. Why old yeast cells stop dividing and die is unclear. We found that age-induced accumulation of the G1/S-phase inhibitor Whi5 and defects in G1/S cyclin transcription cause cell cycle delays and genomic instability that r...

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Main Authors: Neurohr, Gabriel, Terry, Rachel L., Sandikci, Arzu, Zou, Ke, Li, Hao, Amon, Angelika B
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Language:English
Published: Cold Spring Harbor Laboratory 2020
Online Access:https://hdl.handle.net/1721.1/126009
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author Neurohr, Gabriel
Terry, Rachel L.
Sandikci, Arzu
Zou, Ke
Li, Hao
Amon, Angelika B
author2 Massachusetts Institute of Technology. Department of Biology
author_facet Massachusetts Institute of Technology. Department of Biology
Neurohr, Gabriel
Terry, Rachel L.
Sandikci, Arzu
Zou, Ke
Li, Hao
Amon, Angelika B
author_sort Neurohr, Gabriel
collection MIT
description Budding yeast cells produce a finite number of daughter cells before they die. Why old yeast cells stop dividing and die is unclear. We found that age-induced accumulation of the G1/S-phase inhibitor Whi5 and defects in G1/S cyclin transcription cause cell cycle delays and genomic instability that result in cell death. We further identified extrachromosomal rDNA (ribosomal DNA) circles (ERCs) to cause the G1/S cyclin expression defect in old cells. Spontaneous segregation of Whi5 and ERCs into daughter cells rejuvenates old mothers, but daughters that inherit these aging factors die rapidly. Our results identify deregulation of the G1/S-phase transition as the proximal cause of age-induced proliferation decline and cell death in budding yeast.
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spelling mit-1721.1/1260092022-10-01T16:44:25Z Deregulation of the G1/S-phase transition is the proximal cause of mortality in old yeast mother cells Neurohr, Gabriel Terry, Rachel L. Sandikci, Arzu Zou, Ke Li, Hao Amon, Angelika B Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Budding yeast cells produce a finite number of daughter cells before they die. Why old yeast cells stop dividing and die is unclear. We found that age-induced accumulation of the G1/S-phase inhibitor Whi5 and defects in G1/S cyclin transcription cause cell cycle delays and genomic instability that result in cell death. We further identified extrachromosomal rDNA (ribosomal DNA) circles (ERCs) to cause the G1/S cyclin expression defect in old cells. Spontaneous segregation of Whi5 and ERCs into daughter cells rejuvenates old mothers, but daughters that inherit these aging factors die rapidly. Our results identify deregulation of the G1/S-phase transition as the proximal cause of age-induced proliferation decline and cell death in budding yeast. 2020-06-29T14:09:46Z 2020-06-29T14:09:46Z 2018-07 2018-06 2019-11-26T15:12:02Z Article http://purl.org/eprint/type/JournalArticle 0890-9369 1549-5477 https://hdl.handle.net/1721.1/126009 Neurohr, Gabriel E. et al. "Deregulation of the G1/S-phase transition is the proximal cause of mortality in old yeast mother cells." Genes and Development 32, 15-16 (July 2018): 1075-1084 © 2018 Neurohr et al en http://dx.doi.org/10.1101/gad.312140.118 Genes and Development Creative Commons Attribution NonCommercial License 4.0 https://creativecommons.org/licenses/by-nc/4.0/ application/pdf Cold Spring Harbor Laboratory Cold Spring Harbor Laboratory Press
spellingShingle Neurohr, Gabriel
Terry, Rachel L.
Sandikci, Arzu
Zou, Ke
Li, Hao
Amon, Angelika B
Deregulation of the G1/S-phase transition is the proximal cause of mortality in old yeast mother cells
title Deregulation of the G1/S-phase transition is the proximal cause of mortality in old yeast mother cells
title_full Deregulation of the G1/S-phase transition is the proximal cause of mortality in old yeast mother cells
title_fullStr Deregulation of the G1/S-phase transition is the proximal cause of mortality in old yeast mother cells
title_full_unstemmed Deregulation of the G1/S-phase transition is the proximal cause of mortality in old yeast mother cells
title_short Deregulation of the G1/S-phase transition is the proximal cause of mortality in old yeast mother cells
title_sort deregulation of the g1 s phase transition is the proximal cause of mortality in old yeast mother cells
url https://hdl.handle.net/1721.1/126009
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