Regulatory Networks Revealed by Transcriptional Profiling of Damaged Saccharomyces cerevisiae Cells: Rpn4 Links Base Excision Repair with Proteasomes

doi:10.1128/MCB.20.21.8157-8167.2000

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Molecular and Cellular Biology, November 2000, p. 8157-8167, Vol. 20, No. 21
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Regulatory Networks Revealed by Transcriptional Profiling of Damaged Saccharomyces cerevisiae Cells: Rpn4 Links Base Excision Repair with Proteasomes

Scott A. Jelinsky,¹ Preston Estep,² George M. Church,² and Leona D. Samson¹^,^*

Cancer Cell Biology, Harvard School of Public Health,¹ and Department of Genetics, Harvard Medical School,² Boston, Massachusetts 02115

Received 31 May 2000/Returned for modification 13 July 2000/Accepted 4 August 2000

Exposure to carcinogenic alkylating agents, oxidizing agents, and ionizing radiation modulates transcript levels for overone third of Saccharomyces cerevisiae's 6,200 genes. Computationalanalysis delineates groups of coregulated genes whose upstreamregions bear known and novel regulatory sequence motifs. One groupof coregulated genes contain a number of DNA excision repair genes(including the MAG1 3-methyladenine DNA glycosylase gene) anda large selection of protein degradation genes. Moreover, transcriptionof these genes is modulated by the proteasome-associated proteinRpn4, most likely via its binding to MAG1 upstream repressor sequence2-like elements, that turn out to be almost identical to the recentlyidentified 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 whosetranscription is influenced byRpn4p.

^* Corresponding author. Mailing address: Cancer Cell Biology, Harvard School of Public Health, 665 Huntington Avenue, Boston,MA 02115. Phone: (617) 432-1085. Fax: (617) 432-0400. E-mail:lsamson{at}hsph.harvard.edu.

Molecular and Cellular Biology, November 2000, p. 8157-8167, Vol. 20, No. 21
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

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