ArticleeLife2020
Suppressing proteasome mediated processing of topoisomerase II DNA-protein complexes preserves genome integrity.
Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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.
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
28 citing papers in PubMed, 44 citations in OpenAlex.
- MYC modulates TOP2A diffusion to promote substrate detection and activity.Nature communications · 2026Article
- From the TOP: Formation, recognition and resolution of topoisomerase DNA protein crosslinks.DNA repair · 2024Review
- Genome Instability Induced by Topoisomerase Misfunction.International journal of molecular sciences · 2024Review
- DNA damage-induced proteasome phosphorylation controls substrate recognition and facilitates DNA repair.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Inhibition of topoisomerase 2 catalytic activity impacts the integrity of heterochromatin and repetitive DNA and leads to interlinks between clustered repeats.Nature communications · 2024Article
- SUMO and the DNA damage response.Biochemical Society transactions · 2024Review
- RNF4 sustains Myc-driven tumorigenesis by facilitating DNA replication.The Journal of clinical investigation · 2024Article
- RAD54L2-mediated DNA damage avoidance pathway specifically preserves genome integrity in response to topoisomerase 2 poisons.Science advances · 2023Article
- Coinhibition of topoisomerase 1 and BRD4-mediated pause release selectively kills pancreatic cancer via readthrough transcription.Science advances · 2023Article
- FACS-based genome-wide CRISPR screens define key regulators of DNA damage signaling pathways.Molecular cell · 2023Article
- Quantitative Detection of DNA-Protein Crosslinks and Their Post-Translational Modifications.Journal of visualized experiments : JoVE · 2023Article
- Genome-Wide CRISPR Screens Reveal ZATT as a Synthetic Lethal Target of TOP2-Poison Etoposide That Can Act in a TDP2-Independent Pathway.International journal of molecular sciences · 2023Article
- Untangling the roles of TOP2A and TOP2B in transcription and cancer.Science advances · 2022Review
- TOP1 CAD-seq: A protocol to map catalytically engaged topoisomerase 1 in human cells.STAR protocols · 2022Article
- Recurrent mutations in topoisomerase IIα cause a previously undescribed mutator phenotype in human cancers.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The repair of topoisomerase 2 cleavage complexes in Arabidopsis.The Plant cell · 2022Article
- MYC assembles and stimulates topoisomerases 1 and 2 in a "topoisome".Molecular cell · 2022Article
- Article
- Etoposide, an anticancer drug involved in therapy-related secondary leukemia: Enzymes at play.Translational oncology · 2021Review
- DNA damage and regulation of protein homeostasis.DNA repair · 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
11 authors at 2 institutions in 1 country.
Funding
Abstract
Topoisomerase II (TOP2) relieves topological stress in DNA by introducing double-strand breaks (DSBs) via a transient, covalently linked TOP2 DNA-protein intermediate, termed TOP2 cleavage complex (TOP2cc). TOP2ccs are normally rapidly reversible, but can be stabilized by TOP2 poisons, such as the chemotherapeutic agent etoposide (ETO). TOP2 poisons have shown significant variability in their therapeutic effectiveness across different cancers for reasons that remain to be determined. One potential explanation for the differential cellular response to these drugs is in the manner by which cells process TOP2ccs. Cells are thought to remove TOP2ccs primarily by proteolytic degradation followed by DNA DSB repair. Here, we show that proteasome-mediated repair of TOP2cc is highly error-prone. Pre-treating primary splenic mouse B-cells with proteasome inhibitors prevented the proteolytic processing of trapped TOP2ccs, suppressed the DNA damage response (DDR) and completely protected cells from ETO-induced genome instability, thereby preserving cellular viability. When degradation of TOP2cc was suppressed, the TOP2 enzyme uncoupled itself from the DNA following ETO washout, in an error-free manner. This suggests a potential mechanism of developing resistance to topoisomerase poisons by ensuring rapid TOP2cc reversal.
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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.