Gene interactions in the DNA damage-response pathway identified by genome-wide RNA-interference analysis of synthetic lethalityvan Haaften, G., Vastenhouw, N. L., Nollen, E. A. A., Plasterk, R. H. A. & Tijsterman, M., 31-Aug-2004, In : Proceedings of the National Academy of Sciences of the United States of America. 101, 35, p. 12992-12996 5 p.
Research output: Contribution to journal › Article › Academic › peer-review
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.
|Number of pages||5|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Publication status||Published - 31-Aug-2004|
- Animals, Animals, Genetically Modified, Caenorhabditis elegans, DNA Damage, DNA Repair, RNA Interference, Journal Article, Research Support, Non-U.S. Gov't