Specific transcriptional responses induced by 8-methoxypsoralen and UVA in yeast

• Published in: FEMS yeast research 2007-09, Vol.7 (6), p.866-878
• Main Authors: Dardalhon, Michèle, Lin, Waka, Nicolas, Alain, Averbeck, Dietrich
• Format: Article
• Language: English
• Subjects: 8‐methoxypsoralen (8‐MOP) plus UVA; Cell Cycle - drug effects; Cell Cycle - radiation effects; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA Damage; DNA microarrays; DNA Repair; Gene expression; Gene Expression Regulation, Fungal - drug effects; Gene Expression Regulation, Fungal - radiation effects; Genomes; Genotoxicity; Kinases; Methoxsalen - pharmacology; microarrays; Oligonucleotide Array Sequence Analysis; Photosensitizing Agents - pharmacology; Rad51 Recombinase - metabolism; Saccharomyces cerevisiae; Saccharomyces cerevisiae - drug effects; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae - radiation effects; Saccharomyces cerevisiae Proteins - metabolism; Time Factors; Transcription activation; Ultraviolet radiation; Ultraviolet Rays
• ISSN: 1567-1356; 1567-1364
• DOI: 10.1111/j.1567-1364.2007.00270.x

Abstract Treatment of eukaryotic cells with 8-methoxypsoralen plus UVA irradiation (8-MOP/UVA) induces pyrimidine monoadducts and interstrand crosslinks and initiates a cascade of events leading to cytotoxic, mutagenic and carcinogenic responses. Transcriptional activation plays an important part in these responses. Our previous study in Saccharomyces cerevisiae showed that the repair of these lesions involves the transient formation of DNA double-strand breaks and the enhanced expression of landmark DNA damage response genes such as RAD51, RNR2 and DUN1, as well as the Mec1/Rad53 kinase signaling cascade. We have now used DNA microarrays to examine genome-wide transcriptional changes produced after induction of 8-MOP/UVA photolesions. We found that 128 genes were strongly induced and 29 genes strongly repressed. Modifications in gene expression concern numerous biological processes. Compared to other genotoxic treatments, c. 42% of the response genes were specific to 8-MOP/UVA treatment. In addition to common DNA damage response genes and genes induced by environmental stresses, a large fraction of 8-MOP/UVA response genes correspond to membrane-related functions.