ArticleProceedings of the National Academy of Sciences of the United States of America2016
Overexpression screens identify conserved dosage chromosome instability genes in yeast and human cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 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
54 citing papers in PubMed, 82 citations in OpenAlex.
- Burst of aneuploidy: a cost of adaptation driven by breakdown of cell cycle control.Molecular systems biology · 2026Article
- Article
- Genomic epidemiology ofmBio · 2025Article
- Deep structure-function analysis of the endonuclease Mus81 with dominant mutational scanning.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Identification of targetable vulnerabilities of PLK1-overexpressing cancers by synthetic dosage lethality.Cell genomics · 2025Article
- Phosphate-dependent nuclear export via a non-classical NES class recognized by exportin Msn5.Nature communications · 2025Article
- Evolutionary adaptation to hyperstable microtubules selectively targets tubulins and is empowered by the spindle assembly checkpoint.Cell reports · 2025Article
- TDP1 phosphorylation by CDK1 in mitosis promotes MUS81-dependent repair of trapped Top1-DNA covalent complexes.The EMBO journal · 2024Article
- Review
- A cyclin D1 intrinsically disordered domain accesses modified histone motifs to govern gene transcription.Oncogenesis · 2024Article
- Natural Products and Their Derivatives as Inhibitors of the DNA Repair Enzyme Tyrosyl-DNA Phosphodiesterase 1.International journal of molecular sciences · 2023Review
- N-terminal domain of tyrosyl-DNA phosphodiesterase I regulates topoisomerase I-induced toxicity in cells.Scientific reports · 2023Article
- Elevated TAF12 Expression Predicts Poor Prognosis in Glioma Patients: Evidence from Bioinformatic and Immunohistochemical Analyses.Biomolecules · 2022Article
- The Renaissance of CDK Inhibitors in Breast Cancer Therapy: An Update on Clinical Trials and Therapy Resistance.Cancers · 2022Review
- A phylogenetically-restricted essential cell cycle progression factor in the human pathogen Candida albicans.Nature communications · 2022Article
- Yeast as a Model to Find New Drugs and Drug Targets forInternational journal of molecular sciences · 2022Review
- Synthetic lethal interactions of DEAD/H-box helicases as targets for cancer therapy.Frontiers in oncology · 2022Review
- VID22 counteracts G-quadruplex-induced genome instability.Nucleic acids research · 2021Article
- The Rpd3-Complex Regulates Expression of Multiple Cell Surface Recycling Factors in Yeast.International journal of molecular sciences · 2021Article
- Chromosomal Instability in Acute Myeloid Leukemia.Cancers · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
Somatic copy number amplification and gene overexpression are common features of many cancers. To determine the role of gene overexpression on chromosome instability (CIN), we performed genome-wide screens in the budding yeast for yeast genes that cause CIN when overexpressed, a phenotype we refer to as dosage CIN (dCIN), and identified 245 dCIN genes. This catalog of genes reveals human orthologs known to be recurrently overexpressed and/or amplified in tumors. We show that two genes, TDP1, a tyrosyl-DNA-phosphdiesterase, and TAF12, an RNA polymerase II TATA-box binding factor, cause CIN when overexpressed in human cells. Rhabdomyosarcoma lines with elevated human Tdp1 levels also exhibit CIN that can be partially rescued by siRNA-mediated knockdown of TDP1 Overexpression of dCIN genes represents a genetic vulnerability that could be leveraged for selective killing of cancer cells through targeting of an unlinked synthetic dosage lethal (SDL) partner. Using SDL screens in yeast, we identified a set of genes that when deleted specifically kill cells with high levels of Tdp1. One gene was the histone deacetylase RPD3, for which there are known inhibitors. Both HT1080 cells overexpressing hTDP1 and rhabdomyosarcoma cells with elevated levels of hTdp1 were more sensitive to histone deacetylase inhibitors valproic acid (VPA) and trichostatin A (TSA), recapitulating the SDL interaction in human cells and suggesting VPA and TSA as potential therapeutic agents for tumors with elevated levels of hTdp1. The catalog of dCIN genes presented here provides a candidate list to identify genes that cause CIN when overexpressed in cancer, which can then be leveraged through SDL to selectively target tumors.
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.