DNA damage induces the expression of many genes proposed to enhance DNA repair capacities. We investigated the mechanism by which DNA damage induces transcription of RNR3, a subunft of ribonucieotkfe reductase. Five compiementation groups of DNA-damage uninducible (dun) mutants were identified. Each is sensitive to DNA damage. dun7 mutants are also defective for RNR7 and RNR2 induction but are proficient for induction of other genes, defining the existence of at least two distinct DNA damage induction pathways. DUN1 encodes a nuclear protein kinase that is also a phosphoprotein. Phosphoryiation of Dun1 increases in response to DNA damage in a Dunl-dependent manner, suggesting an increase in autophosphoryiation activity. These results establish the existence of a eukaryotic SOS response regulated by protein phosphoryiation. introduction

Work from many laboratories has contributed to the concept that in response to DNA damage, ceils induce the expression of genes that facilitate the repair of such lesions. This response is essential for an organism to adapt to life-threatening environmental conditions and to duplicate its genetic material with the highest fidelity (for reviews see Walker, 1985; Herriich et al., 1992). This sensory network is well understood in Escherichia coli. Treatment of E. coli with agents that damage DNAor block replication induces a set of physiological responses that have collectively been called the SOS response (Fladman, 1974). These responses promote cell survival, and blocking them genetically leads to DNA damage sensitivity. Many genes that are transcriptionally activated in response to DNA damage have been identified, including several involved in excision repair, recombinational repair, SOS repression, mutagenesis, and cell cycle arrest. The molecular mechanism of this response involves autoproteolysis of a common repressor, LexA, by a form of the RecA protein activated by DNA damage (for review see Walker, 1985).