Ultraviolet radiation (UVR) is one of the most common mutagens that humans are exposed to and the levels and frequency of exposure is a primary determinant of melanoma risk. In melanocytes, a number of signalling pathways have evolved to counter the damaging effects of UVR exposure. Amongst them is the MC1R G-protein coupled receptor that co-ordinates both melanin synthesis and induces post-UVR DNA repair when stimulated by its ligand α-MSH that signals via cAMP induction. Recently, the anti-microbial peptide β-defensin 3 (HBD3) has also been identified as one of the most highly induced genes in the skin following UVR exposure and has since emerged as an alternative agonist of the MC1R pathway that signals largely via MAPK. We are interested in exploring the mechanisms by which MC1R facilitates DNA repair and have previously identified the rapid and transient induction of the NR4A family of orphan nuclear receptors upon α-MSH stimulation in melanocytes. The induction of NR4A2 appears to be crucial for the ability of the MC1R pathway in enhancing DNA repair capacity that is independent of NR4A2 transcriptional function. Using fluorescence imaging, we have revealed that upon UVR irradiation, NR4A2 translocates to distinct nuclear foci by a mechanism requiring both p38-mediated phosphorylation and the involvement of poly-(ADP-ribose)-polymerase activity. Furthermore, our recent works show that NR4A2 co-localise and interact with proteins involved in the recognition and repair of DNA. Our findings indicate that NR4A2 represent a novel component of DNA damage response, placing it as an interesting candidate for understanding the mechanisms that underpin genomic maintenance and cyto-protection following UVR-induced carcinogenesis that have direct relevance to melanoma formation.