Transcriptome analysis of Aspergillus nidulans exposed to camptothecin-induced DNA damage

Iran Malavazi, Marcela Savoldi, Sônia Marli Zingaretti Di Mauro, Carlos Frederico Martins Menck, Steven D. Harris, Maria Helena De Souza Goldman, Gustavo Henrique Goldman

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

We have used an Aspergillus nidulans macroarray carrying sequences of 2,787 genes from this fungus to monitor gene expression of both wild-type and uvsBATR (the homologue of the ATR gene) deletion mutant strains in a time course exposure to camptothecin (CPT). The results revealed a total of 1,512 and 1,700 genes in the wild-type and uvsBATR deletion mutant strains that displayed a statistically significant difference at at least one experimental time point. We characterized six genes that have increased mRNA expression in the presence of CPT in the wild-type strain relative to the uvsBATR mutant strain: fhdA (encoding a forkhead-associated domain protein), tprA (encoding a hypothetical protein that contains a tetratrico peptide repeat), mshA (encoding a MutS homologue involved in mismatch repair), phbA (encoding a prohibitin homologue), uvsCRAD51 (the homologue of the RAD51 gene), and cshA (encoding a homologue of the excision repair protein ERCC-6 [Cockayne's syndrome protein]). The induced transcript levels of these genes in the presence of CPT require uvsBATR. These genes were deleted, and surprisingly, only the ΔuvsC mutant strain was sensitive to CPT; however, the others displayed sensitivity to a range of DNA-damaging and oxidative stress agents. These results indicate that the selected genes when inactivated display very complex and heterogeneous sensitivity behavior during growth in the presence of agents that directly or indirectly cause DNA damage. Moreover, with the exception of UvsC, deletion of each of these genes partially suppressed the sensitivity of the ΔuvsB strain to menadione and paraquat. Our results provide the first insight into the overall complexity of the response to DNA damage in filamentous fungi and suggest that multiple pathways may act in parallel to mediate DNA repair.

Original languageEnglish (US)
Pages (from-to)1688-1704MP
JournalEukaryotic Cell
Volume5
Issue number10
DOIs
StatePublished - Oct 2006

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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    Malavazi, I., Savoldi, M., Di Mauro, S. M. Z., Menck, C. F. M., Harris, S. D., De Souza Goldman, M. H., & Goldman, G. H. (2006). Transcriptome analysis of Aspergillus nidulans exposed to camptothecin-induced DNA damage. Eukaryotic Cell, 5(10), 1688-1704MP. https://doi.org/10.1128/EC.00167-06