1. Genome-Wide Dynamic Evaluation of the UV-Induced DNA Damage Response
- Author
-
Gordon J. Bean, Trey Ideker, Elizabeth A. Winzeler, Brenton Munson, Erica Silva, Philipp A. Jaeger, Katherine Licon, and Manuel Michaca
- Subjects
Mitochondrial DNA ,Saccharomyces cerevisiae Proteins ,DNA Repair ,Ultraviolet Rays ,DNA damage ,Saccharomyces cerevisiae ,Mutant ,QH426-470 ,DNA damage response ,Genome ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,ultraviolet radiation response ,high-throughput screen ,Molecular Biology ,Gene ,Genetics (clinical) ,030304 developmental biology ,0303 health sciences ,biology ,Mutant Screen Report ,biology.organism_classification ,Cell biology ,Transfer RNA ,030217 neurology & neurosurgery ,DNA Damage ,Genetic screen - Abstract
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.
- Published
- 2020