title: The csnD/csnE signalosome genes are involved in the Aspergillus nidulans DNA damage response.
abstract: The signalosome (CSN) is a conserved multiprotein complex involved in regulation of eukaryotic development and is also required to activate ribonucleotide reductase for DNA synthesis. In Aspergillus nidulans, csnD/csnE are key regulators of sexual development. Here, we investigated whether the csnD/csnE genes are involved in the DNA damage response in this fungus. The growth of the csnD/csnE deletion mutants was reduced by subinhibitory concentrations of hydroxyurea, camptothecin, 4-nitroquinoline oxide, and methyl methanesulfonate. A. nidulans increases csnD/csnE mRNA levels when it is challenged by different DNA-damaging agents. There is no significant transcriptional induction of the csnE promoter fused with lacZ gene in the presence of DNA-damaging agents, suggesting that increased mRNA accumulation is due to increased mRNA stability. Septation was not inhibited in the csnD/csnE deletion mutants while DeltauvsB DeltacsnE presented an increase in septation upon DNA damage caused by methyl methanesulfonate, suggesting that uvsB(ATR) and csnE genetically interact during checkpoint-dependent inhibition of septum formation. The double DeltacsnD/DeltacsnE DeltanpkA mutants were more sensitive to DNA-damaging agents than were the respective single mutants. Our results suggest that csnD/csnE genes are involved in the DNA damage response and that NpkA and UvsB(ATR) genetically interact with the signalosome.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto and Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, São Paulo, 1404-903 Brazil.
authors.forename: Joel Fernandes
authors.initials: JF
authors.lastname: Lima
authors.forename: Iran
authors.initials: I
authors.lastname: Malavazi
authors.forename: Marcia Regina
authors.initials: MR
authors.lastname: von Zeska Kress Fagundes
authors.forename: Marcela
authors.initials: M
authors.lastname: Savoldi
authors.forename: Maria Helena S
authors.initials: MH
authors.lastname: Goldman
authors.forename: Elke
authors.initials: E
authors.lastname: Schwier
authors.forename: Gerhard H
authors.initials: GH
authors.lastname: Braus
authors.forename: Gustavo Henrique
authors.initials: GH
authors.lastname: Goldman
mesh_terms: D001233:Aspergillus nidulans / Q000235:genetics* / Q000502:physiology; D000075686:COP9 Signalosome Complex; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair / Q000235:genetics* / Q000502:physiology; D005800:Genes, Fungal; D046912:Multiprotein Complexes / Q000235:genetics*; D010447:Peptide Hydrolases / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012098:Reproduction / Q000235:genetics; D012264:Ribonucleotide Reductases / Q000096:biosynthesis / Q000235:genetics
chemical_list: D046912:Multiprotein Complexes; D012333:RNA, Messenger; D012264:Ribonucleotide Reductases; D010447:Peptide Hydrolases; D000075686:COP9 Signalosome Complex