ArticlePLoS computational biology2013
Synthetic lethality between gene defects affecting a single non-essential molecular pathway with reversible steps.
Article in PLoS computational biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
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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.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Dynamic Assemblies in Genome Maintenance.Advances in experimental medicine and biology · 2026Review
- Fission yeast Rad54 prevents intergenerational buildup of Rad51 aggregates in proliferating cells.Life science alliance · 2025Article
- Investigating synthetic lethality and PARP inhibitor resistance in pancreatic cancer through enantiomer differential activity.Cell death discovery · 2025Article
- A moving target for drug discovery: Structure activity relationship and many genome (de)stabilizing functions of the RAD52 protein.DNA repair · 2022Review
- RNAi Screening Uncovers a Synthetic Sick Interaction between CtIP and the BARD1 Tumor Suppressor.Cells · 2022Article
- Using Synthetic Genetic Interactions in Candida glabrata as a Novel Method to Detect Genes with Roles in Antifungal Drug Resistance.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Article
- Synthetic Lethality through the Lens of Medicinal Chemistry.Journal of medicinal chemistry · 2020Review
- FEN1 endonuclease as a therapeutic target for human cancers with defects in homologous recombination.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Systematical Analysis of the Protein Targets of Lactoferricin B and Histatin-5 Using Yeast Proteome Microarrays.International journal of molecular sciences · 2019Article
- Dynamic Processing of Displacement Loops during Recombinational DNA Repair.Molecular cell · 2019Article
- Review: Precision medicine and driver mutations: Computational methods, functional assays and conformational principles for interpreting cancer drivers.PLoS computational biology · 2019Review
- Synthetic Lethal Networks for Precision Oncology: Promises and Pitfalls.Journal of molecular biology · 2018Review
- Article
- Small-Molecule Inhibitors Targeting DNA Repair and DNA Repair Deficiency in Research and Cancer Therapy.Cell chemical biology · 2017Review
- Pathways and Mechanisms that Prevent Genome Instability inGenetics · 2017Review
- A genetic network that suppresses genome rearrangements in Saccharomyces cerevisiae and contains defects in cancers.Nature communications · 2016Article
- Regulation of recombination and genomic maintenance.Cold Spring Harbor perspectives in biology · 2015Review
- The structural basis for cancer treatment decisions.Oncotarget · 2014Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Systematic analysis of synthetic lethality (SL) constitutes a critical tool for systems biology to decipher molecular pathways. The most accepted mechanistic explanation of SL is that the two genes function in parallel, mutually compensatory pathways, known as between-pathway SL. However, recent genome-wide analyses in yeast identified a significant number of within-pathway negative genetic interactions. The molecular mechanisms leading to within-pathway SL are not fully understood. Here, we propose a novel mechanism leading to within-pathway SL involving two genes functioning in a single non-essential pathway. This type of SL termed within-reversible-pathway SL involves reversible pathway steps, catalyzed by different enzymes in the forward and backward directions, and kinetic trapping of a potentially toxic intermediate. Experimental data with recombinational DNA repair genes validate the concept. Mathematical modeling recapitulates the possibility of kinetic trapping and revealed the potential contributions of synthetic, dosage-lethal interactions in such a genetic system as well as the possibility of within-pathway positive masking interactions. Analysis of yeast gene interaction and pathway data suggests broad applicability of this novel concept. These observations extend the canonical interpretation of synthetic-lethal or synthetic-sick interactions with direct implications to reconstruct molecular pathways and improve therapeutic approaches to diseases such as cancer.
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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.