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A Global Perspective of the Genetic Basis for Carbonyl Stress Resistance
The accumulation of protein adducts caused by carbonyl stress (CS) is a hallmark of cellular aging and other diseases, yet the detailed cellular effects of this universal phenomena are poorly understood. An understanding of the global effects of CS will provide insight into disease mechanisms and ca...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Genetics Society of America
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276133/ https://www.ncbi.nlm.nih.gov/pubmed/22384333 http://dx.doi.org/10.1534/g3.111.000505 |
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author | Hoon, Shawn Gebbia, Marinella Costanzo, Michael Davis, Ronald W. Giaever, Guri Nislow, Corey |
author_facet | Hoon, Shawn Gebbia, Marinella Costanzo, Michael Davis, Ronald W. Giaever, Guri Nislow, Corey |
author_sort | Hoon, Shawn |
collection | PubMed |
description | The accumulation of protein adducts caused by carbonyl stress (CS) is a hallmark of cellular aging and other diseases, yet the detailed cellular effects of this universal phenomena are poorly understood. An understanding of the global effects of CS will provide insight into disease mechanisms and can guide the development of therapeutics and lifestyle changes to ameliorate their effects. To identify cellular functions important for the response to carbonyl stress, multiple genome-wide genetic screens were performed using two known inducers of CS. We found that different cellular functions were required for resistance to stress induced by methylglyoxal (MG) and glyoxal (GLY). Specifically, we demonstrate the importance of macromolecule catabolism processes for resistance to MG, confirming and extending known mechanisms of MG toxicity, including modification of DNA, RNA, and proteins. Combining our results with related studies that examined the effects of ROS allowed a comprehensive view of the diverse range of cellular functions affected by both oxidative and carbonyl stress. To understand how these diverse cellular functions interact, we performed a quantitative epistasis analysis by creating multimutant strains from those individual genes required for glyoxal resistance. This analysis allowed us to define novel glyoxal-dependent genetic interactions. In summary, using multiple genome-wide approaches provides an effective approach to dissect the poorly understood effects of glyoxal in vivo. These data, observations, and comprehensive dataset provide 1) a comprehensive view of carbonyl stress, 2) a resource for future studies in other cell types, and 3) a demonstration of how inexpensive cell-based assays can identify complex gene-environment toxicities. |
format | Online Article Text |
id | pubmed-3276133 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Genetics Society of America |
record_format | MEDLINE/PubMed |
spelling | pubmed-32761332012-03-01 A Global Perspective of the Genetic Basis for Carbonyl Stress Resistance Hoon, Shawn Gebbia, Marinella Costanzo, Michael Davis, Ronald W. Giaever, Guri Nislow, Corey G3 (Bethesda) Investigation The accumulation of protein adducts caused by carbonyl stress (CS) is a hallmark of cellular aging and other diseases, yet the detailed cellular effects of this universal phenomena are poorly understood. An understanding of the global effects of CS will provide insight into disease mechanisms and can guide the development of therapeutics and lifestyle changes to ameliorate their effects. To identify cellular functions important for the response to carbonyl stress, multiple genome-wide genetic screens were performed using two known inducers of CS. We found that different cellular functions were required for resistance to stress induced by methylglyoxal (MG) and glyoxal (GLY). Specifically, we demonstrate the importance of macromolecule catabolism processes for resistance to MG, confirming and extending known mechanisms of MG toxicity, including modification of DNA, RNA, and proteins. Combining our results with related studies that examined the effects of ROS allowed a comprehensive view of the diverse range of cellular functions affected by both oxidative and carbonyl stress. To understand how these diverse cellular functions interact, we performed a quantitative epistasis analysis by creating multimutant strains from those individual genes required for glyoxal resistance. This analysis allowed us to define novel glyoxal-dependent genetic interactions. In summary, using multiple genome-wide approaches provides an effective approach to dissect the poorly understood effects of glyoxal in vivo. These data, observations, and comprehensive dataset provide 1) a comprehensive view of carbonyl stress, 2) a resource for future studies in other cell types, and 3) a demonstration of how inexpensive cell-based assays can identify complex gene-environment toxicities. Genetics Society of America 2011-08-01 /pmc/articles/PMC3276133/ /pubmed/22384333 http://dx.doi.org/10.1534/g3.111.000505 Text en Copyright © 2011 Hoon et al. http://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Unported License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Investigation Hoon, Shawn Gebbia, Marinella Costanzo, Michael Davis, Ronald W. Giaever, Guri Nislow, Corey A Global Perspective of the Genetic Basis for Carbonyl Stress Resistance |
title | A Global Perspective of the Genetic Basis for Carbonyl Stress Resistance |
title_full | A Global Perspective of the Genetic Basis for Carbonyl Stress Resistance |
title_fullStr | A Global Perspective of the Genetic Basis for Carbonyl Stress Resistance |
title_full_unstemmed | A Global Perspective of the Genetic Basis for Carbonyl Stress Resistance |
title_short | A Global Perspective of the Genetic Basis for Carbonyl Stress Resistance |
title_sort | global perspective of the genetic basis for carbonyl stress resistance |
topic | Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276133/ https://www.ncbi.nlm.nih.gov/pubmed/22384333 http://dx.doi.org/10.1534/g3.111.000505 |
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