Specific transcriptional responses induced by 8-methoxypsoralen and UVA in yeast.
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.
Dardalhon
Michèle
M
Institut Curie Section de Recherche, UMR2027 CNRS/I.C., INSERM, Centre Universitaire d'Orsay, Orsay Cedex, France. michele.dardalhon@curie.u-psud.fr
Lin
Waka
W
Nicolas
Alain
A
Averbeck
Dietrich
D
D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects* / Q000528:radiation effects*; D008730:Methoxsalen / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D017319:Photosensitizing Agents / Q000494:pharmacology*; D051135:Rad51 Recombinase / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013997:Time Factors; D014466:Ultraviolet Rays
D017319:Photosensitizing Agents; D029701:Saccharomyces cerevisiae Proteins; C495151:RAD51 protein, S cerevisiae; D051135:Rad51 Recombinase; D008730:Methoxsalen