Researchers Uncover Genes Linked to DNA Damage Response

NEW YORK, Jan. 4 — Researchers at Boston's Dana Farber Cancer Institute and Germany's Max Planck Institute have discovered 23 genes in Caenorhabditis elegans that are connected to the DNA damage response, a mechanism implicated in many types of human cancer.

The research, published in the current issue of the Science, shows that 11 of the 23 are completely new, and 12 are orthologs of known genes in other organisms.

Led by Dana Farber's Marc Vidal, the researchers combined protein-protein interaction mapping with large-scale phenotypic analysis to identify the genes. To find the orthologs, Vidal's team used known DDR proteins in BLAST searches against the C. elegans proteome, identifying 75 candidates that were then used to generate a protein-interaction map. They then used high-throughput RNA-mediated interference for each corresponding gene and scored DDR process defects through large-scale phenotypic analysis.

The lab, located in the genetics department at Dana Farber, focuses on functional genomics and protein interactions in C. elegans. Lab projects include developing high-throughput techniques to clone and annotate worm open-reading frames, to identify protein interactions, to use in silico approaches to analyze functionality, and to validate interactions in vivo. The lab has partnerships for this research with Invitrogen and Genome Therapeutics.

The findings indicate that functional genomic mapping of model organisms can be a useful tool in understanding human cancers, the authors write.