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Nuclear Lipid Droplet Birth during Replicative Stress

The nuclear membrane defines the boundaries that confine, protect and shape the genome. As such, its blebbing, ruptures and deformations are known to compromise the integrity of genetic material. Yet, drastic transitions of the nuclear membrane such as its invagination towards the nucleoplasm or its...

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Autores principales: Kumanski, Sylvain, Forey, Romain, Cazevieille, Chantal, Moriel-Carretero, María
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9105094/
https://www.ncbi.nlm.nih.gov/pubmed/35563696
http://dx.doi.org/10.3390/cells11091390
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author Kumanski, Sylvain
Forey, Romain
Cazevieille, Chantal
Moriel-Carretero, María
author_facet Kumanski, Sylvain
Forey, Romain
Cazevieille, Chantal
Moriel-Carretero, María
author_sort Kumanski, Sylvain
collection PubMed
description The nuclear membrane defines the boundaries that confine, protect and shape the genome. As such, its blebbing, ruptures and deformations are known to compromise the integrity of genetic material. Yet, drastic transitions of the nuclear membrane such as its invagination towards the nucleoplasm or its capacity to emit nuclear lipid droplets (nLD) have not been evaluated with respect to their impact on genome dynamics. To begin assessing this, in this work we used Saccharomyces cerevisiae as a model to ask whether a selection of genotoxins can trigger the formation of nLD. We report that nLD formation is not a general feature of all genotoxins, but of those engendering replication stress. Exacerbation of endogenous replication stress by genetic tools also elicited nLD formation. When exploring the lipid features of the nuclear membrane at the base of this emission, we revealed a link with the unsaturation profile of its phospholipids and, for the first time, of its sterol content. We propose that stressed replication forks may stimulate nLD birth by anchoring to the inner nuclear membrane, provided that the lipid context is adequate. Further, we point to a transcriptional feed-back process that counteracts the membrane’s proneness to emit nLD. With nLD representing platforms onto which genome-modifying reactions can occur, our findings highlight them as important players in the response to replication stress.
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spelling pubmed-91050942022-05-14 Nuclear Lipid Droplet Birth during Replicative Stress Kumanski, Sylvain Forey, Romain Cazevieille, Chantal Moriel-Carretero, María Cells Article The nuclear membrane defines the boundaries that confine, protect and shape the genome. As such, its blebbing, ruptures and deformations are known to compromise the integrity of genetic material. Yet, drastic transitions of the nuclear membrane such as its invagination towards the nucleoplasm or its capacity to emit nuclear lipid droplets (nLD) have not been evaluated with respect to their impact on genome dynamics. To begin assessing this, in this work we used Saccharomyces cerevisiae as a model to ask whether a selection of genotoxins can trigger the formation of nLD. We report that nLD formation is not a general feature of all genotoxins, but of those engendering replication stress. Exacerbation of endogenous replication stress by genetic tools also elicited nLD formation. When exploring the lipid features of the nuclear membrane at the base of this emission, we revealed a link with the unsaturation profile of its phospholipids and, for the first time, of its sterol content. We propose that stressed replication forks may stimulate nLD birth by anchoring to the inner nuclear membrane, provided that the lipid context is adequate. Further, we point to a transcriptional feed-back process that counteracts the membrane’s proneness to emit nLD. With nLD representing platforms onto which genome-modifying reactions can occur, our findings highlight them as important players in the response to replication stress. MDPI 2022-04-20 /pmc/articles/PMC9105094/ /pubmed/35563696 http://dx.doi.org/10.3390/cells11091390 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kumanski, Sylvain
Forey, Romain
Cazevieille, Chantal
Moriel-Carretero, María
Nuclear Lipid Droplet Birth during Replicative Stress
title Nuclear Lipid Droplet Birth during Replicative Stress
title_full Nuclear Lipid Droplet Birth during Replicative Stress
title_fullStr Nuclear Lipid Droplet Birth during Replicative Stress
title_full_unstemmed Nuclear Lipid Droplet Birth during Replicative Stress
title_short Nuclear Lipid Droplet Birth during Replicative Stress
title_sort nuclear lipid droplet birth during replicative stress
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9105094/
https://www.ncbi.nlm.nih.gov/pubmed/35563696
http://dx.doi.org/10.3390/cells11091390
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