通过全基因组RNA干扰合成致死分析鉴定的DNA损伤反应途径中的基因相互作用。
Gene interactions in the DNA damage-response pathway identified by genome-wide RNA-interference analysis of synthetic lethality.
作者信息
van Haaften Gijs, Vastenhouw Nadine L, Nollen Ellen A A, Plasterk Ronald H A, Tijsterman Marcel
机构信息
Hubrecht Laboratory, Center for Biomedical Genetics, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.
出版信息
Proc Natl Acad Sci U S A. 2004 Aug 31;101(35):12992-6. doi: 10.1073/pnas.0403131101. Epub 2004 Aug 23.
Abstract
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.
摘要
在此，我们描述了对多细胞生物秀丽隐杆线虫中合成基因相互作用的系统性搜索。我们建立了一种高通量方法，通过全基因组RNA干扰来确定合成基因相互作用，并鉴定出了保护生殖系免受DNA双链断裂所需的基因。除了已知的DNA修复蛋白，如秀丽隐杆线虫中TopBP1、RPA2和RAD51的直系同源物外，还鉴定出了8个以前与双链断裂反应无关的基因。敲低这些基因会增加对电离辐射和喜树碱的敏感性，并导致染色体不分离增加。所有这些基因在人类中都有直系同源物，可能在人类致癌过程中发挥作用。
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