A UV response that involves the Ras proteins and AP-1 transcription factors has recently been described in mammals and yeast. To test whether an equivalent response exists in plants, we monitored the expression of Arabidopsis histidinol dehydrogenase gene (HDH), a homologue of the yeast HIS4 gene, which is strongly induced by UV light and is a target of the transcriptional activator Gcn4. We show that HDH mRNA levels increase specifically in response to UV-B light. Only small increases were detected upon exposure to other wavelengths. To isolate plant genes involved in this UV response, a gcn4 mutant was transfected with an Arabidopsis thaliana cDNA library. A new type of nucleotide diphosphate kinase (NDPK Ia) with a significant homology to the human tumor suppressor protein Nm23 rescued the gcn4 phenotype. NDPK Ia specifically binds to the HIS4 promoter in vitro and induces HIS4 transcription in yeast. In Arabidopsis, the NDPK Ia protein is located in the nucleus and cytosol. Expression studies in seedlings revealed that the level of NDPK Ia mRNA, like that of HDH, increases in response to UV-B light. It appears that NDPK Ia and HDH are components of a novel UV-responsive pathway in A. thaliana.