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...
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Oxford University Press
2020-09-01
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Online Access: | http://g3journal.org/lookup/doi/10.1534/g3.120.401417 |
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doaj-a8a81772825e407eb16bf0125f5b60b62021-07-02T13:11:20ZengOxford University PressG3: Genes, Genomes, Genetics2160-18362020-09-011092981298810.1534/g3.120.4014178Genome-Wide Dynamic Evaluation of the UV-Induced DNA Damage ResponseErica SilvaManuel MichacaBrenton MunsonGordon J. BeanPhilipp A. JaegerKatherine LiconElizabeth A. WinzelerTrey IdekerGenetic 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.http://g3journal.org/lookup/doi/10.1534/g3.120.401417ultraviolet radiation responsedna damage responsehigh-throughput screen |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Erica Silva Manuel Michaca Brenton Munson Gordon J. Bean Philipp A. Jaeger Katherine Licon Elizabeth A. Winzeler Trey Ideker |
spellingShingle |
Erica Silva Manuel Michaca Brenton Munson Gordon J. Bean Philipp A. Jaeger Katherine Licon Elizabeth A. Winzeler Trey Ideker Genome-Wide Dynamic Evaluation of the UV-Induced DNA Damage Response G3: Genes, Genomes, Genetics ultraviolet radiation response dna damage response high-throughput screen |
author_facet |
Erica Silva Manuel Michaca Brenton Munson Gordon J. Bean Philipp A. Jaeger Katherine Licon Elizabeth A. Winzeler Trey Ideker |
author_sort |
Erica Silva |
title |
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_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_sort |
genome-wide dynamic evaluation of the uv-induced dna damage response |
publisher |
Oxford University Press |
series |
G3: Genes, Genomes, Genetics |
issn |
2160-1836 |
publishDate |
2020-09-01 |
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. |
topic |
ultraviolet radiation response dna damage response high-throughput screen |
url |
http://g3journal.org/lookup/doi/10.1534/g3.120.401417 |
work_keys_str_mv |
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1721329248407388160 |