A genome-wide screen in Saccharomyces cerevisiae for genes affecting UV radiation sensitivity

The recent completion of the deletion of essentially all of the ORFs in yea st is an important new resource for identifying the phenotypes of unknown g enes. Each ORF is replaced with a cassette containing unique tag sequences that allow rapid parallel analysis of strains in a pool by using hybridizat ion to a high-density oligonucleotide array. We examined the utility of thi s system to identify genes conferring resistance to UV irradiation by using a pool of 4,627 individual homozygous deletion strains (representing delet ions of all nonessential genes). We identified most of the nonessential gen es previously shown to be involved in nuclecitide excision repair, in cell cycle checkpoints, in homologous recombination, and in postreplication repa ir after UV damage. We also identified and individually confirmed, by repla cing the genes, three new genes, to our knowledge not previously reported t o confer UV sensitivity when deleted. Two of these newly identified genes h ave human orthologs associated with cancer, demonstrating the potential of this system to uncover human genes affecting sensitivity to DNA-damaging ag ents and genes potentially involved in cancer formation.