Mediator 17 (MED17) is a subunit of the Mediator complex that regulates transcription initiation in eukaryotic organisms. In yeast and humans, MED17 also participates in DNA repair, physically interacting with proteins of the nucleotide excision DNA repair system, but this function in plants has not been investigated. We studied the role of MED17 in Arabidopsis plants exposed to UV-B radiation. Our results demonstrate that med17 and OE MED17 plants have altered responses to UV-B, and that MED17 participates in various aspects of the DNA damage response (DDR). Comparison of the med17 transcriptome with that of wild-type (WT) plants showed that almost one-third of transcripts with altered expression in med17 plants were also changed by UV-B exposure in WT plants. Increased sensitivity to DNA damage after UV-B in med17 plants could result from the altered regulation of UV-B responsive transcripts but MED17 also physically interacts with DNA repair proteins, suggesting a direct role of this Mediator subunit during repair. Finally, we show that MED17 is necessary to regulate the DDR activated by ataxia telangiectasia and Rad3 related (ATR), and that programmed cell death 5 (PDCD5) overexpression reverts the deficiencies in DDR shown in med17 mutants. Our data demonstrate that MED17 is an important regulator of DDR after UV-B irradiation in Arabidopsis.