ArticleMolecular biology of the cell2009
Synthetic lethal genetic interactions that decrease somatic cell proliferation in Caenorhabditis elegans identify the alternative RFC CTF18 as a candidate cancer drug target.
Article in Molecular biology of the cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- A global genetic interaction map of a human cell reveals conserved principles of genetic networks.bioRxiv : the preprint server for biology · 2025Article
- Mapping of DDX11 genetic interactions defines sister chromatid cohesion as the major dependency.G3 (Bethesda, Md.) · 2024Article
- The Fork Protection Complex: A Regulatory Hub at the Head of the Replisome.Sub-cellular biochemistry · 2022Article
- Mapping Synthetic Dosage Lethal Genetic Interactions in Saccharomyces cerevisiae.Methods in molecular biology (Clifton, N.J.) · 2021Article
- MRE11-RAD50-NBS1 promotes Fanconi Anemia R-loop suppression at transcription-replication conflicts.Nature communications · 2019Article
- Shugoshin Is Essential for Meiotic Prophase Checkpoints in C. elegans.Current biology : CB · 2018Article
- Review
- Article
- Discovering Genetic Interactions in Large-Scale Association Studies by Stage-wise Likelihood Ratio Tests.PLoS genetics · 2015Article
- A Synthetic Lethal Screen Identifies a Role for Lin-44/Wnt in C. elegans Embryogenesis.PloS one · 2015Article
- Overexpression of cohesion establishment factor DSCC1 through E2F in colorectal cancer.PloS one · 2014Article
- Synthetic lethal targeting of superoxide dismutase 1 selectively kills RAD54B-deficient colorectal cancer cells.Genetics · 2013Article
- Article
- An evolutionarily conserved synthetic lethal interaction network identifies FEN1 as a broad-spectrum target for anticancer therapeutic development.PLoS genetics · 2013Article
- R-loop-mediated genome instability in mRNA cleavage and polyadenylation mutants.Genes & development · 2012Article
- The Caenorhabditis elegans THO complex is required for the mitotic cell cycle and development.PloS one · 2012Article
- Cross-species functional genomic analysis identifies resistance genes of the histone deacetylase inhibitor valproic acid.PloS one · 2012Article
- Synthetic lethality of cohesins with PARPs and replication fork mediators.PLoS genetics · 2012Article
- Predisposition to cancer caused by genetic and functional defects of mammalian Atad5.PLoS genetics · 2011Article
- The complete spectrum of yeast chromosome instability genes identifies candidate CIN cancer genes and functional roles for ASTRA complex components.PLoS genetics · 2011Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Somatic mutations causing chromosome instability (CIN) in tumors can be exploited for selective killing of cancer cells by knockdown of second-site genes causing synthetic lethality. We tested and statistically validated synthetic lethal (SL) interactions between mutations in six Saccharomyces cerevisiae CIN genes orthologous to genes mutated in colon tumors and five additional CIN genes. To identify which SL interactions are conserved in higher organisms and represent potential chemotherapeutic targets, we developed an assay system in Caenorhabditis elegans to test genetic interactions causing synthetic proliferation defects in somatic cells. We made use of postembryonic RNA interference and the vulval cell lineage of C. elegans as a readout for somatic cell proliferation defects. We identified SL interactions between members of the cohesin complex and CTF4, RAD27, and components of the alternative RFC(CTF18) complex. The genetic interactions tested are highly conserved between S. cerevisiae and C. elegans and suggest that the alternative RFC components DCC1, CTF8, and CTF18 are ideal therapeutic targets because of their mild phenotype when knocked down singly in C. elegans. Furthermore, the C. elegans assay system will contribute to our knowledge of genetic interactions in a multicellular animal and is a powerful approach to identify new cancer therapeutic targets.
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