ArticleGenetics2014
Synthetic cytotoxicity: digenic interactions with TEL1/ATM mutations reveal sensitivity to low doses of camptothecin.
Article in Genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- Review
- Identifying digenic disease genes via machine learning in the Undiagnosed Diseases Network.American journal of human genetics · 2021Article
- Complex Mechanisms of Antimony Genotoxicity in Budding Yeast Involves Replication and Topoisomerase I-Associated DNA Lesions, Telomere Dysfunction and Inhibition of DNA Repair.International journal of molecular sciences · 2021Article
- In Silico Inference of Synthetic Cytotoxic Interactions from Paclitaxel Responses.International journal of molecular sciences · 2021Article
- Identification of synthetic chemosensitivity genes paired with BRAF for BRAF/MAPK inhibitors.Scientific reports · 2020Article
- Article
- Synthetic lethality and cancer.Nature reviews. Genetics · 2017Review
- Hypermutation signature reveals a slippage and realignment model of translesion synthesis by Rev3 polymerase in cisplatin-treated yeast.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- The Genetic Basis of Mendelian Phenotypes: Discoveries, Challenges, and Opportunities.American journal of human genetics · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Many tumors contain mutations that confer defects in the DNA-damage response and genome stability. DNA-damaging agents are powerful therapeutic tools that can differentially kill cells with an impaired DNA-damage response. The response to DNA damage is complex and composed of a network of coordinated pathways, often with a degree of redundancy. Tumor-specific somatic mutations in DNA-damage response genes could be exploited by inhibiting the function of a second gene product to increase the sensitivity of tumor cells to a sublethal concentration of a DNA-damaging therapeutic agent, resulting in a class of conditional synthetic lethality we call synthetic cytotoxicity. We used the Saccharomyces cerevisiae nonessential gene-deletion collection to screen for synthetic cytotoxic interactions with camptothecin, a topoisomerase I inhibitor, and a null mutation in TEL1, the S. cerevisiae ortholog of the mammalian tumor-suppressor gene, ATM. We found and validated 14 synthetic cytotoxic interactions that define at least five epistasis groups. One class of synthetic cytotoxic interaction was due to telomere defects. We also found that at least one synthetic cytotoxic interaction was conserved in Caenorhabditis elegans. We have demonstrated that synthetic cytotoxicity could be a useful strategy for expanding the sensitivity of certain tumors to DNA-damaging therapeutics.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.