Regulation of the ribonucleotide reductase small subunit gene by DNA-damaging agents in Dictyostelium discoideum.
In Escherichia coli, yeast and mammalian cells, the genes encoding ribonucleotide reductase, an essential enzyme for de novo DNA synthesis, are up-regulated in response to DNA damaging agents. We have examined the response of the rnrB gene, encoding the small subunit of ribonucleotide reductase in Dictyostelium discoideum, to DNA damaging agents. We show here that the accumulation of rnrB transcript is increased in response to methyl methane sulfonate, 4-nitroquinoline-1-oxide and irradiation with UV-light, but not to the ribonucleotide reductase inhibitor hydroxyurea. This response is rapid, transient and independent of protein synthesis. Moreover, cells from different developmental stages are able to respond to the drug in a similar fashion, regardless of the basal level of expression of the rnrB gene. We have defined the cis -acting elements of the rnrB promoter required for the response to methyl methane sulfonate and 4-nitroquinoline-1-oxide by deletion analysis. Our results indicate that there is one element, named box C, that can confer response to both drugs. Two other boxes, box A and box D, specifically conferred response to methyl methane sulfonate and 4-nitroquinoline-1-oxide, respectively.
Gaudet
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Department of Chemistry, Concordia University, 1455 de Maisonneuve Boulevard W., Montreal, Quebec H3G 1M8, Canada.
Tsang
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A
D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology; D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D004249:DNA Damage / Q000235:genetics* / Q000528:radiation effects; D004023:Dictyostelium / Q000187:drug effects / Q000201:enzymology / Q000235:genetics* / Q000254:growth & development; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000528:radiation effects; D017125:Genes, Protozoan / Q000235:genetics; D006918:Hydroxyurea / Q000494:pharmacology; D007700:Kinetics; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D017384:Sequence Deletion; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000187:drug effects / Q000528:radiation effects
D012333:RNA, Messenger; D015112:4-Nitroquinoline-1-oxide; D003513:Cycloheximide; D008741:Methyl Methanesulfonate; D012264:Ribonucleotide Reductases; D006918:Hydroxyurea