The DNA damage response (DDR) is essential for normal cell function and for tumour suppression. In January 4 Science, Simon Boulton and colleagues at the Dana-Farber Cancer Institute, Boston, report a strategy to identify novel DDR genes (Science 2002, 295:127-131).

They combined functional genomics approaches — that is protein-protein interaction mapping and high-throughput phenotype analysis — to investigate DDR in Caenorhabditis elegans. They chose 75 worm genes representing orthologs of proteins involved in nucleotide-excision repair (NER), mismatch repair (MS), base-excision repair (BER) or non-homologous end joining (NHEJ) and tested them in the yeast two-hybrid protein-protein interaction assay.

The team confirmed interactions observed in other species and found new interacting partners. Proteome-wide interaction screening identified a large number of 'interologs', enabling Boulton et al. to construct a DDR protein-interaction map. They validated candidate genes using the 'RNAi by feeding' method, and looked for DDR phenotypes...