Gene interactions in the DNA damage-response pathway identified by genome-wide RNA-interference analysis of synthetic lethality.
Here, we describe a systematic search for synthetic gene interactions in a multicellular organism, the nematode Caenorhabditis elegans. We established a high-throughput method to determine synthetic gene interactions by genome-wide RNA interference and identified genes that are required to protect the germ line against DNA double-strand breaks. Besides known DNA-repair proteins such as the C. elegans orthologs of TopBP1, RPA2, and RAD51, eight genes previously unassociated with a double-strand-break response were identified. Knockdown of these genes increased sensitivity to ionizing radiation and camptothecin and resulted in increased chromosomal nondisjunction. All genes have human orthologs that may play a role in human carcinogenesis.
Hubrecht Laboratory, Center for Biomedical Genetics, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.
Gijs
G
van Haaften
Nadine L
NL
Vastenhouw
Ellen A A
EA
Nollen
Ronald H A
RH
Plasterk
Marcel
M
Tijsterman
D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology; D004249:DNA Damage / Q000235:genetics / Q000502:physiology; D004260:DNA Repair / Q000235:genetics* / Q000502:physiology; D034622:RNA Interference / Q000502:physiology*