Combined Functional Genomic Maps of the C. elegans DNA Damage Response

• Published in: Science (American Association for the Advancement of Science) Vol. 295; no. 5552; pp. 127 - 131
• Main Authors: Boulton, Simon J., Gartner, Anton, Reboul, Jérôme, Vaglio, Philippe, Dyson, Nick, Hill, David E., Vidal, Marc
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 04.01.2002; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Algorithms; Animals; Base Sequence; BCL3 gene; Biological and medical sciences; Caenorhabditis elegans; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans - physiology; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - physiology; Cancer; Cancer research; Chromosome Mapping; Computational Biology; Deoxyribonucleic acid; DNA; DNA damage; DNA Damage - genetics; DNA repair; DNA Repair - genetics; DNA Replication; Evaluation; Fundamental and applied biological sciences. Psychology; Gamma Rays; Gene Silencing; Genes; Genes, Helminth; Genome; Genomics; Germ cells; Human genome; Humans; Interaction Process Analysis; Medical research; Medicine, Experimental; Molecular and cellular biology; Oncology, Experimental; Open Reading Frames; Phenotype; Phenotypes; Protein interaction mapping; Proteins; Proteome; Proto-Oncogene Proteins - genetics; Recombination, Genetic; Sertoli cells; Transcription Factors; Two-Hybrid System Techniques; Worms; Yeast; Yeast (Food product); United States
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1065986

Many human cancers originate from defects in the DNA damage response (DDR). Although much is known about this process, it is likely that additional DDR genes remain to be discovered. To identify such genes, we used a strategy that combines protein-protein interaction mapping and large-scale phenotypic analysis in Caenorhabditis elegans. Together, these approaches identified 12 worm DDR orthologs and 11 novel DDR genes. One of these is the putative ortholog of hBCL3, a gene frequently altered in chronic lymphocytic leukemia. Thus, the combination of functional genomic mapping approaches in model organisms may facilitate the identification and characterization of genes involved in cancer and, perhaps, other human diseases.