title: Yap1 and Skn7 genetically interact with Rad51 in response to oxidative stress and DNA double-strand break in Saccharomyces cerevisiae.
abstract: Reactive oxygen species (ROS)-mediated DNA adducts as well as DNA strand breaks are highly mutagenic leading to genomic instability and tumorigenesis. DNA damage repair pathways and oxidative stress response signaling have been proposed to be highly associated, but the underlying interaction remains unknown. In this study, we employed mutant strains lacking Rad51, the homolog of E. coli RecA recombinase, and Yap1 or Skn7, two major transcription factors responsive to ROS, to examine genetic interactions between double-strand break (DSB) repair proteins and cellular redox regulators in budding yeast Saccharomyces cerevisiae. Abnormal expression of YAP1 or SKN7 aggravated the mutation rate of rad51 mutants and their sensitivity to DSB- or ROS-generating reagents. Rad51 deficiency exacerbated genome instability in the presence of increased levels of ROS, and the accumulation of DSB lesions resulted in elevated intracellular ROS levels. Our findings suggest that evident crosstalk between DSB repair pathways and ROS signaling proteins contributes to cell survival and maintenance of genome integrity in response to genotoxic stress.
authors.affiliation: Department of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Dae Gwan
authors.initials: DG
authors.lastname: Yi
authors.affiliation: College of Pharmacy, Duksung Women's University, Seoul 01369, Republic of Korea; Innovative Drug Center, Duksung Women's University, Seoul 01369, Republic of Korea.
authors.forename: Myung Ju
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Duksung Women's University, Seoul 01369, Republic of Korea; Innovative Drug Center, Duksung Women's University, Seoul 01369, Republic of Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Choi
authors.affiliation: College of Pharmacy, Duksung Women's University, Seoul 01369, Republic of Korea; Innovative Drug Center, Duksung Women's University, Seoul 01369, Republic of Korea.
authors.forename: Jihyun
authors.initials: J
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Duksung Women's University, Seoul 01369, Republic of Korea; Innovative Drug Center, Duksung Women's University, Seoul 01369, Republic of Korea.
authors.forename: Joohee
authors.initials: J
authors.lastname: Jung
authors.affiliation: Department of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Won-Ki
authors.initials: WK
authors.lastname: Huh
authors.affiliation: College of Pharmacy, Duksung Women's University, Seoul 01369, Republic of Korea; Innovative Drug Center, Duksung Women's University, Seoul 01369, Republic of Korea. Electronic address: whchung23@duksung.ac.kr.
authors.forename: Woo-Hyun
authors.initials: WH
authors.lastname: Chung
mesh_terms: D002470:Cell Survival; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004260:DNA Repair; D004271:DNA, Fungal / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D042822:Genomic Instability; D059765:Homologous Recombination; D006861:Hydrogen Peroxide / Q000494:pharmacology; D059645:Mutation Rate; D018384:Oxidative Stress; D010269:Paraquat / Q000494:pharmacology; D051135:Rad51 Recombinase / Q000172:deficiency / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D017382:Reactive Oxygen Species; C083962:SKN7 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C086677:YAP1 protein, S cerevisiae; D006861:Hydrogen Peroxide; C495151:RAD51 protein, S cerevisiae; D051135:Rad51 Recombinase; D010269:Paraquat
keywords: Double-strand break; Genome stability; Homologous recombination; Rad51; Reactive oxygen species; Skn7; Yap1