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Genetics. 2005 Nov;171(3):1003-15. Epub 2005 Aug 3.

The csnD/csnE signalosome genes are involved in the Aspergillus nidulans DNA damage response.

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1
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.

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.

PMID:
16079239
PMCID:
PMC1456808
DOI:
10.1534/genetics.105.041376
[Indexed for MEDLINE]
Free PMC Article
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