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Genome-Wide Dynamic Evaluation of the UV-Induced DNA Damage Response
Genetic screens in Saccharomyces cerevisiae have allowed for the identification of many genes as sensors or effectors of DNA damage, typically by comparing the fitness of genetic mutants in the presence or absence of DNA-damaging treatments. However, these static screens overlook the dynamic nature...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Genetics Society of America
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466999/ https://www.ncbi.nlm.nih.gov/pubmed/32732306 http://dx.doi.org/10.1534/g3.120.401417 |
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author | Silva, Erica Michaca, Manuel Munson, Brenton Bean, Gordon J. Jaeger, Philipp A. Licon, Katherine Winzeler, Elizabeth A. Ideker, Trey |
author_facet | Silva, Erica Michaca, Manuel Munson, Brenton Bean, Gordon J. Jaeger, Philipp A. Licon, Katherine Winzeler, Elizabeth A. Ideker, Trey |
author_sort | Silva, Erica |
collection | PubMed |
description | Genetic screens in Saccharomyces cerevisiae have allowed for the identification of many genes as sensors or effectors of DNA damage, typically by comparing the fitness of genetic mutants in the presence or absence of DNA-damaging treatments. However, these static screens overlook the dynamic nature of DNA damage response pathways, missing time-dependent or transient effects. Here, we examine gene dependencies in the dynamic response to ultraviolet radiation-induced DNA damage by integrating ultra-high-density arrays of 6144 diploid gene deletion mutants with high-frequency time-lapse imaging. We identify 494 ultraviolet radiation response genes which, in addition to recovering molecular pathways and protein complexes previously annotated to DNA damage repair, include components of the CCR4-NOT complex, tRNA wobble modification, autophagy, and, most unexpectedly, 153 nuclear-encoded mitochondrial genes. Notably, mitochondria-deficient strains present time-dependent insensitivity to ultraviolet radiation, posing impaired mitochondrial function as a protective factor in the ultraviolet radiation response. |
format | Online Article Text |
id | pubmed-7466999 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Genetics Society of America |
record_format | MEDLINE/PubMed |
spelling | pubmed-74669992020-09-14 Genome-Wide Dynamic Evaluation of the UV-Induced DNA Damage Response Silva, Erica Michaca, Manuel Munson, Brenton Bean, Gordon J. Jaeger, Philipp A. Licon, Katherine Winzeler, Elizabeth A. Ideker, Trey G3 (Bethesda) Mutant Screen Report Genetic screens in Saccharomyces cerevisiae have allowed for the identification of many genes as sensors or effectors of DNA damage, typically by comparing the fitness of genetic mutants in the presence or absence of DNA-damaging treatments. However, these static screens overlook the dynamic nature of DNA damage response pathways, missing time-dependent or transient effects. Here, we examine gene dependencies in the dynamic response to ultraviolet radiation-induced DNA damage by integrating ultra-high-density arrays of 6144 diploid gene deletion mutants with high-frequency time-lapse imaging. We identify 494 ultraviolet radiation response genes which, in addition to recovering molecular pathways and protein complexes previously annotated to DNA damage repair, include components of the CCR4-NOT complex, tRNA wobble modification, autophagy, and, most unexpectedly, 153 nuclear-encoded mitochondrial genes. Notably, mitochondria-deficient strains present time-dependent insensitivity to ultraviolet radiation, posing impaired mitochondrial function as a protective factor in the ultraviolet radiation response. Genetics Society of America 2020-07-30 /pmc/articles/PMC7466999/ /pubmed/32732306 http://dx.doi.org/10.1534/g3.120.401417 Text en Copyright © 2020 Silva et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Mutant Screen Report Silva, Erica Michaca, Manuel Munson, Brenton Bean, Gordon J. Jaeger, Philipp A. Licon, Katherine Winzeler, Elizabeth A. Ideker, Trey Genome-Wide Dynamic Evaluation of the UV-Induced DNA Damage Response |
title | Genome-Wide Dynamic Evaluation of the UV-Induced DNA Damage Response |
title_full | Genome-Wide Dynamic Evaluation of the UV-Induced DNA Damage Response |
title_fullStr | Genome-Wide Dynamic Evaluation of the UV-Induced DNA Damage Response |
title_full_unstemmed | Genome-Wide Dynamic Evaluation of the UV-Induced DNA Damage Response |
title_short | Genome-Wide Dynamic Evaluation of the UV-Induced DNA Damage Response |
title_sort | genome-wide dynamic evaluation of the uv-induced dna damage response |
topic | Mutant Screen Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466999/ https://www.ncbi.nlm.nih.gov/pubmed/32732306 http://dx.doi.org/10.1534/g3.120.401417 |
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