DUN1 ENCODES A PROTEIN-KINASE THAT CONTROLS THE DNA-DAMAGE RESPONSE IN YEAST

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 subunit of ribonucleotide reductase. Five complementation groups of DNA-damage uninducible (dun) mutants were identified. Each is sensitive to DNA damage. dun1 mutants are also defective for RNR1 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. Phosphorylation of Dun1 increases in response to DNA damage in a Dun1-dependent manner, suggesting an increase in autophosphorylation activity. These results establish the existence of a eukaryotic SOS response regulated by protein phosphorylation.