title: Transcriptional response of yeast to aflatoxin B1: recombinational repair involving RAD51 and RAD1.
abstract: The potent carcinogen aflatoxin B(1) is a weak mutagen but a strong recombinagen in Saccharomyces cerevisiae. Aflatoxin B(1) exposure greatly increases frequencies of both heteroallelic recombination and chromosomal translocations. We analyzed the gene expression pattern of diploid cells exposed to aflatoxin B(1) using high-density oligonucleotide arrays comprising specific probes for all 6218 open reading frames. Among 183 responsive genes, 46 are involved in either DNA repair or in control of cell growth and division. Inducible growth control genes include those in the TOR signaling pathway and SPO12, whereas PKC1 is downregulated. Eleven of the 15 inducible DNA repair genes, including RAD51, participate in recombination. Survival and translocation frequencies are reduced in the rad51 diploid after aflatoxin B(1) exposure. In mec1 checkpoint mutants, aflatoxin B(1) exposure does not induce RAD51 expression or increase translocation frequencies; however, when RAD51 is constitutively overexpressed in the mec1 mutant, aflatoxin B(1) exposure increased translocation frequencies. Thus the transcriptional profile after aflatoxin B(1) exposure may elucidate the genotoxic properties of aflatoxin B(1).
authors.affiliation: Institute of Toxicology, Swiss Federal Institute of Technology ETH, CH-8603 Schwerzenbach, Switzerland.
authors.forename: Monika U
authors.initials: MU
authors.lastname: Keller-Seitz
authors.forename: Ulrich
authors.initials: U
authors.lastname: Certa
authors.forename: Christian
authors.initials: C
authors.lastname: Sengstag
authors.forename: Friedrich E
authors.initials: FE
authors.lastname: Würgler
authors.forename: Mingzeng
authors.initials: M
authors.lastname: Sun
authors.forename: Michael
authors.initials: M
authors.lastname: Fasullo
mesh_terms: D000199:Actins / Q000235:genetics; D016604:Aflatoxin B1 / Q000633:toxicity*; D001483:Base Sequence; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics; D045643:DNA Repair Enzymes; D004271:DNA, Fungal / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D005800:Genes, Fungal / Q000187:drug effects; D008954:Models, Biological; D009153:Mutagens / Q000633:toxicity; D009154:Mutation; D051135:Rad51 Recombinase; D011995:Recombination, Genetic / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014178:Translocation, Genetic / Q000187:drug effects
chemical_list: C465210:Act1 protein, S cerevisiae; D000199:Actins; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D009153:Mutagens; D029701:Saccharomyces cerevisiae Proteins; D016604:Aflatoxin B1; C495151:RAD51 protein, S cerevisiae; D051135:Rad51 Recombinase; D004720:Endonucleases; C069266:RAD1 protein, S cerevisiae; D045643:DNA Repair Enzymes