Damage in worms

Combined functional genomics approaches help to identify novel genes involved in the DNA damage response pathway in nematodes.

Jonathan Weitzman(

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...

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