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Gene interactions in the DNA damage-response pathway identified by genome-wide RNA-interference analysis of synthetic lethality

van 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.

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DOI

  • Gijs van Haaften
  • Nadine L Vastenhouw
  • Ellen A A Nollen
  • Ronald H A Plasterk
  • Marcel Tijsterman

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.

Original languageEnglish
Pages (from-to)12992-12996
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number35
Publication statusPublished - 31-Aug-2004

    Keywords

  • Animals, Animals, Genetically Modified, Caenorhabditis elegans, DNA Damage, DNA Repair, RNA Interference, Journal Article, Research Support, Non-U.S. Gov't

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