Transcriptional response to nitrosative stress in Saccharomyces cerevisiae.
Nitric oxide and NO-derived species (RNS) are defence molecules with broad antimicrobial activity. Microorganisms have developed strategies to sense RNS and counteract their damaging effects. We used Saccharomyces cerevisiae, harbouring a deletion of YHB1 that encodes the main NO scavenger enzyme, to study consequences of RNS exposure on whole-genome transcriptional response. The expression of > 700 genes was altered on RNS treatment. No major role for ROS-scavenging enzymes was found, and the respiratory chain, the main site of ROS production, had only minor involvement in the RNS-induced stress. The changes were generally transient and also found after treatment with the respiratory inhibitor myxothiazol. However, 117 genes showed a persistent response that was not observed after myxothiazol treatment. Of these, genes of the glutathione and DNA repair systems, iron homeostasis and transport were found to be upregulated. Severe repression of genes of respiratory chain enzymes was observed. Many of these genes are known to be regulated by the transcription factor Hap1p, suggesting that RNS might interfere with Hap1p activity. We showed also that Msn2/4p and Yap1p, key regulators of the response to general stress and oxidative stress, respectively, played a role in mediating the RNS-induced response.
Horan
Susannah
S
Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK.
Bourges
Ingrid
I
Meunier
Brigitte
B
D004260:DNA Repair / Q000502:physiology; D004789:Enzyme Activation; D005227:Fatty Acids / Q000096:biosynthesis; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects / Q000502:physiology; D007501:Iron / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D012331:RNA, Fungal / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013261:Sterols / Q000096:biosynthesis; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*
D005227:Fatty Acids; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D012331:RNA, Fungal; D029701:Saccharomyces cerevisiae Proteins; D013261:Sterols; D014157:Transcription Factors; C094210:2,2'-(hydroxynitrosohydrazono)bis-ethanamine; D009569:Nitric Oxide; D007501:Iron