Ultraviolet radiation (UVR) is a major environmental factor in the development of melanoma and defects in mechanisms that respond to UVR damage in melanocytes must be major contributors to the development of melanoma. The recently sequenced melanoma genomes have revealed high level of UV signature mutations but there is little evidence that known DNA repair mechanisms responding to UV-induced damage are commonly defective in melanomas. We have identified a novel cell cycle response to suberythemal doses of UVR that is commonly defective in melanomas. Suberythemal UVR exposure has several effects on the cell cycle of cells in basal layer of the epidermis. It is strongly mitogenic, driving quiescent basal cells into cycle where they subsequently arrest in G2 phase checkpoint arrest. The G2 phase checkpoint arrest has utilises ATR / Chk1 checkpoint signalling activated by RPA foci associated single strand DNA (ssDNA) which accumulate during S phase as a consequence of WRN helicase-dependent bypass of a small number of unrepaired UVR-induced DNA lesion. WRN is required to prevent replication fork stalling and collapse when the fork machinery encounters these unrepaired lesions. The ssDNA gaps are repaired by a RAD18 dependent mechanism during G2 phase. Loss of this G2 phase response results in increased UV signature mutations. In an effort to fully define the checkpoint and repair responses we have used microarray analysis of polysome preparations from UV-induced G2 phase checkpoint arrested cells to identify genes differentially loaded onto polysomes in the checkpoint arrested cells, indicating genes that are being actively translated into protein, and also performed a SILAC proteomics screen to identify proteins whose levels are significantly altered in the checkpoint arrested cells. These screens have identified several classes of gene/proteins; checkpoint related, repair related, cytoskeletal and mitochrondrial/apoptosis. We have initially pursued the checkpoint and repair genes, and will report the analysis of these and their potential roles in the G2 phase checkpoint and repair response. Identification of all the genes contributing to this response will be critical to understanding the defects in this response in melanoma, and whether it is loss of this response that underlies the increased UV signature mutations found in melanomas.