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  • 标题:Gene interactions in the DNA damage-response pathway identified by genome-wide RNA-interference analysis of synthetic lethality
  • 本地全文:下载
  • 作者:Gijs van Haaften ; Nadine L. Vastenhouw ; Ellen A. A. Nollen
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2004
  • 卷号:101
  • 期号:35
  • 页码:12992-12996
  • DOI:10.1073/pnas.0403131101
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要: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.
  • 关键词:DNA double-strand break ; synthetic gene interactions ; Caenorhabditis elegans
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