Regulatory networks revealed by transcriptional profiling of damaged Saccharomyces cerevisiae cells: Rpn4 links base excision repair with proteasomes.
Exposure to carcinogenic alkylating agents, oxidizing agents, and ionizing radiation modulates transcript levels for over one third of Saccharomyces cerevisiae's 6,200 genes. Computational analysis delineates groups of coregulated genes whose upstream regions bear known and novel regulatory sequence motifs. One group of coregulated genes contain a number of DNA excision repair genes (including the MAG1 3-methyladenine DNA glycosylase gene) and a large selection of protein degradation genes. Moreover, transcription of these genes is modulated by the proteasome-associated protein Rpn4, most likely via its binding to MAG1 upstream repressor sequence 2-like elements, that turn out to be almost identical to the recently identified proteasome-associated control element (G. Mannhaupt, R. Schnall, V. Karpov, I. Vetter, and H. Feldmann, FEBS Lett. 450:27-34, 1999). We have identified a large number of genes whose transcription is influenced by Rpn4p.
Jelinsky
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Cancer Cell Biology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Estep
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Church
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Samson
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D000465:Algorithms; D016000:Cluster Analysis; D003198:Computer Simulation; D003546:Cysteine Endopeptidases / Q000235:genetics*; D045647:DNA Glycosylases; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D008741:Methyl Methanesulfonate; D015233:Models, Statistical; D009097:Multienzyme Complexes / Q000235:genetics*; D009153:Mutagens; D009699:N-Glycosyl Hydrolases / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D046988:Proteasome Endopeptidase Complex; D012333:RNA, Messenger / Q000378:metabolism; D015203:Reproducibility of Results; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D009097:Multienzyme Complexes; D009153:Mutagens; D012333:RNA, Messenger; C119430:RPN4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D008741:Methyl Methanesulfonate; C021565:3-methyladenine-DNA glycosylase; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex