This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Elledge, S J Articles by Davis, R W Search for Related Content PubMed PubMed Citation Articles by Elledge, S J Articles by Davis, R W

 Previous Article  |  Next Article 

Mol Cell Biol. 1989 December; 9(12): 5373-5386

Identification of the DNA damage-responsive element of RNR2 and evidence that four distinct cellular factors bind it.

Department of Biochemistry, Baylor College of Medicine, Houston, Texas 77030.

ABSTRACT

The RNR2 gene encodes the small subunit of ribonucleotide reductase, the enzyme that catalyzes the first step in the pathway for the production of the deoxyribonucleotides needed for DNA synthesis. Transcription of this gene is induced approximately 20-fold in response to environmental stimuli that damage DNA or block DNA replication. Deletion and subcloning analysis identified two, and possibly three, upstream activating sequences (UAS) and one repressing (URS) element in the RNR2 regulatory region. A 42-base-pair (bp) fragment from this region was found to be necessary for proper regulation of RNR2 and to be capable of conferring DNA damage inducibility upon a heterologous promoter. This fragment contained both positively and negatively acting sequences. Four DNA-binding factors interacted with the RNR2 regulatory region. One factor was identified as the GRF1 protein, the product of the RAP1 gene. GRF1 bound to the UAS2 element of RNR2, which was found to be directly adjacent to the 42-bp fragment. UAS2 activity was repressed by the 42-bp fragment. Three other factors bound to the 42-bp fragment; one of these factors, RRF3, had a second binding site in the RNR2 promoter. These factors are likely to mediate the response of RNR2 to DNA damage.

This article has been cited by other articles:

• Cordon-Preciado, V., Ufano, S., Bueno, A. (2006). Limiting amounts of budding yeast Rad53 S-phase checkpoint activity results in increased resistance to DNA alkylation damage. Nucleic Acids Res 34: 5852-5862 [Abstract] [Full Text]  
• Tringe, S. G., Willis, J., Liberatore, K. L., Ruby, S. W. (2006). The WTM Genes in Budding Yeast Amplify Expression of the Stress-Inducible Gene RNR3. Genetics 174: 1215-1228 [Abstract] [Full Text]  
• Cohen, Y., Dardalhon, M., Averbeck, D. (2002). Homologous recombination is essential for RAD51 up-regulation in Saccharomyces cerevisiae following DNA crosslinking damage. Nucleic Acids Res 30: 1224-1232 [Abstract] [Full Text]  
• Yamaguchi, T., Matsuda, K., Sagiya, Y., Iwadate, M., Fujino, M. A., Nakamura, Y., Arakawa, H. (2001). p53R2-dependent Pathway for DNA Synthesis in a p53-regulated Cell Cycle Checkpoint. Cancer Res. 61: 8256-8262 [Abstract] [Full Text]  
• Hassane, D. C., Lee, R. B., Mendenhall, M. D., Pickett, C. L. (2001). Cytolethal Distending Toxin Demonstrates Genotoxic Activity in a Yeast Model. Infect. Immun. 69: 5752-5759 [Abstract] [Full Text]  
• Fikus, M. U., Mieczkowski, P. A., Koprowski, P., Rytka, J., ledziewska-Gójska, E., Ciela, Z. (2000). The Product of the DNA Damage-Inducible Gene of Saccharomyces cerevisiae, DIN7, Specifically Functions in Mitochondria. Genetics 154: 73-81 [Abstract] [Full Text]  
• Sidorova, J. M., Breeden, L. L. (1997). Rad53-dependent phosphorylation of Swi6 and down-regulation of CLN1 and CLN2 transcription occur in response to DNA damage in Saccharomyces cerevisiae. Genes Dev. 11: 3032-3045 [Abstract] [Full Text]  
• Marini, N J, Reed, S I (1992). Direct induction of G1-specific transcripts following reactivation of the Cdc28 kinase in the absence of de novo protein synthesis.. Genes Dev. 6: 557-567 [Abstract]  
• Kurtz, S, Shore, D (1991). RAP1 protein activates and silences transcription of mating-type genes in yeast.. Genes Dev. 5: 616-628 [Abstract]  
• Elledge, S J, Davis, R W (1990). Two genes differentially regulated in the cell cycle and by DNA-damaging agents encode alternative regulatory subunits of ribonucleotide reductase.. Genes Dev. 4: 740-751 [Abstract]