Title: Genome-Wide Dynamic Evaluation of the UV-Induced DNA Damage Response.
Authors: Silva, Erica; Michaca, Manuel; Munson, Brenton; Bean, Gordon J; Jaeger, Philipp A; Licon, Katherine; Winzeler, Elizabeth A; Ideker, Trey
Published In G3 (Bethesda), (2020 09 02)
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.
PubMed ID: 32732306
MeSH Terms: DNA Damage; DNA Repair; Saccharomyces cerevisiae Proteins*/genetics; Saccharomyces cerevisiae Proteins*/metabolism; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/metabolism; Ultraviolet Rays*