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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Main Authors: Erica Silva, Manuel Michaca, Brenton Munson, Gordon J. Bean, Philipp A. Jaeger, Katherine Licon, Elizabeth A. Winzeler, Trey Ideker
Format: Article
Language:English
Published: Oxford University Press 2020-09-01
Series:G3: Genes, Genomes, Genetics
Subjects:
Online Access:http://g3journal.org/lookup/doi/10.1534/g3.120.401417
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spelling 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
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