Combined functional genomic maps of the C. elegans DNA damage response.
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.
Boulton
Simon J
SJ
Dana-Farber Cancer Institute and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Gartner
Anton
A
Reboul
Jérôme
J
Vaglio
Philippe
P
Dyson
Nick
N
Hill
David E
DE
Vidal
Marc
M
D000465:Algorithms; D000818:Animals; D000081242:B-Cell Lymphoma 3 Protein; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D002874:Chromosome Mapping; D019295:Computational Biology; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004261:DNA Replication; D005720:Gamma Rays; D020868:Gene Silencing; D017238:Genes, Helminth; D016678:Genome; D006801:Humans; D016366:Open Reading Frames; D010641:Phenotype; D020543:Proteome; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011995:Recombination, Genetic; D014157:Transcription Factors; D020798:Two-Hybrid System Techniques
D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; D029742:Caenorhabditis elegans Proteins; D020543:Proteome; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors