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

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.

SUBMITTER: van Haaften G

PROVIDER: S-EPMC516506 | biostudies-literature | 2004 Aug

REPOSITORIES: biostudies-literature

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

van Haaften Gijs G Vastenhouw Nadine L NL Nollen Ellen A A EA Plasterk Ronald H A RH Tijsterman Marcel M

Proceedings of the National Academy of Sciences of the United States of America 20040823 35

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-b ...[more]

PMID: 15326288

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