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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 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.

* 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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