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 ribonucl eotide reductase, an essential enzyme for de novo DNA synthesis, are up-reg ulated in response to DNA damaging agents. We have examined the response of the rnrB gene, encoding the small subunit of ribonucleotide reductase in D ictyostelium discoideum, to DNA damaging agents. We show here that the accu mulation of rnrB transcript is increased in response to methyl methane sulf onate, 4-nitroquinoline-1-oxide and irradiation with UV-light, but not to t he ribonucleotide reductase inhibitor hydroxyurea. This response is rapid, transient and independent of protein synthesis. Moreover, cells from differ ent developmental stages are able to respond to the drug in a similar fashi on, regardless of the basal level of expression of the rnrB gene. We have d efined the cis-acting elements of the rnrB promoter required for the respon se to methyl methane sulfonate and 4-nitroquinoline-1-oxide by deletion ana lysis. Our results indicate that there is one element, named box C, that ca n confer response to both drugs. Two other boxes, box A and box D, specific ally conferred response to methyl methane sulfonate and 4-nitroquinoline-1- oxide, respectively.