Transcriptome Analysis of Aspergillus nidulans Exposed to Camptothecin-Induced DNA Damage

Authors

Iran Malazavi, Universidade de Sao Paulo, Sao Paulo, Brazil
Marcela Savoldi, Universidade de Sao Paulo, Sao Paulo, Brazil
Sonia Marla Zingaretti Di Mauro, Universidade de Ribeirao Preto, Sao Paulo, Brazil
Carlos Frederico Martins Menck, Universidade de Sao Paulo, Sao Paulo, Brazil
Steven D. Harris, University of Nebraska-LincolnFollow
Maria Helena de Souza Goldman, Universidade de Sao Paulo, Sao Paulo, Brazil
Gustavo Henrique Goldman, Universidade de Sao Paulo, Sao Paulo, Brazil

Date of this Version

October 2006

Comments

Published in EUKARYOTIC CELL, Oct. 2006, p. 1688–1704 Vol. 5, No. 10. Copyright © 2006, American Society for Microbiology. Used by permission.

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 uvsB^ATR (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 uvsB^ATR 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 uvsB^ATR mutant strain: fhdA (encoding a forkheadassociated 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), uvsC^RAD51 (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 uvsB^ATR. 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.