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The Alkylating Agent Methyl Methanesulfonate Triggers Lipid Alterations at the Inner Nuclear Membrane That Are Independent from Its DNA-Damaging Ability

In order to tackle the study of DNA repair pathways, the physical and chemical agents creating DNA damage, the genotoxins, are frequently employed. Despite their utility, their effects are rarely restricted to DNA, and therefore simultaneously harm other cell biomolecules. Methyl methanesulfonate (M...

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Autores principales: Ovejero, Sara, Soulet, Caroline, Moriel-Carretero, María
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305661/
https://www.ncbi.nlm.nih.gov/pubmed/34299079
http://dx.doi.org/10.3390/ijms22147461
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author Ovejero, Sara
Soulet, Caroline
Moriel-Carretero, María
author_facet Ovejero, Sara
Soulet, Caroline
Moriel-Carretero, María
author_sort Ovejero, Sara
collection PubMed
description In order to tackle the study of DNA repair pathways, the physical and chemical agents creating DNA damage, the genotoxins, are frequently employed. Despite their utility, their effects are rarely restricted to DNA, and therefore simultaneously harm other cell biomolecules. Methyl methanesulfonate (MMS) is an alkylating agent that acts on DNA by preferentially methylating guanine and adenine bases. It is broadly used both in basic genome stability research and as a model for mechanistic studies to understand how alkylating agents work, such as those used in chemotherapy. Nevertheless, MMS exerts additional actions, such as oxidation and acetylation of proteins. In this work, we introduce the important notion that MMS also triggers a lipid stress that stems from and affects the inner nuclear membrane. The inner nuclear membrane plays an essential role in virtually all genome stability maintenance pathways. Thus, we want to raise awareness that the relative contribution of lipid and genotoxic stresses when using MMS may be difficult to dissect and will matter in the conclusions drawn from those studies.
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spelling pubmed-83056612021-07-25 The Alkylating Agent Methyl Methanesulfonate Triggers Lipid Alterations at the Inner Nuclear Membrane That Are Independent from Its DNA-Damaging Ability Ovejero, Sara Soulet, Caroline Moriel-Carretero, María Int J Mol Sci Communication In order to tackle the study of DNA repair pathways, the physical and chemical agents creating DNA damage, the genotoxins, are frequently employed. Despite their utility, their effects are rarely restricted to DNA, and therefore simultaneously harm other cell biomolecules. Methyl methanesulfonate (MMS) is an alkylating agent that acts on DNA by preferentially methylating guanine and adenine bases. It is broadly used both in basic genome stability research and as a model for mechanistic studies to understand how alkylating agents work, such as those used in chemotherapy. Nevertheless, MMS exerts additional actions, such as oxidation and acetylation of proteins. In this work, we introduce the important notion that MMS also triggers a lipid stress that stems from and affects the inner nuclear membrane. The inner nuclear membrane plays an essential role in virtually all genome stability maintenance pathways. Thus, we want to raise awareness that the relative contribution of lipid and genotoxic stresses when using MMS may be difficult to dissect and will matter in the conclusions drawn from those studies. MDPI 2021-07-12 /pmc/articles/PMC8305661/ /pubmed/34299079 http://dx.doi.org/10.3390/ijms22147461 Text en © 2021 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 Communication
Ovejero, Sara
Soulet, Caroline
Moriel-Carretero, María
The Alkylating Agent Methyl Methanesulfonate Triggers Lipid Alterations at the Inner Nuclear Membrane That Are Independent from Its DNA-Damaging Ability
title The Alkylating Agent Methyl Methanesulfonate Triggers Lipid Alterations at the Inner Nuclear Membrane That Are Independent from Its DNA-Damaging Ability
title_full The Alkylating Agent Methyl Methanesulfonate Triggers Lipid Alterations at the Inner Nuclear Membrane That Are Independent from Its DNA-Damaging Ability
title_fullStr The Alkylating Agent Methyl Methanesulfonate Triggers Lipid Alterations at the Inner Nuclear Membrane That Are Independent from Its DNA-Damaging Ability
title_full_unstemmed The Alkylating Agent Methyl Methanesulfonate Triggers Lipid Alterations at the Inner Nuclear Membrane That Are Independent from Its DNA-Damaging Ability
title_short The Alkylating Agent Methyl Methanesulfonate Triggers Lipid Alterations at the Inner Nuclear Membrane That Are Independent from Its DNA-Damaging Ability
title_sort alkylating agent methyl methanesulfonate triggers lipid alterations at the inner nuclear membrane that are independent from its dna-damaging ability
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8305661/
https://www.ncbi.nlm.nih.gov/pubmed/34299079
http://dx.doi.org/10.3390/ijms22147461
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