ArticleProceedings of the National Academy of Sciences of the United States of America2012
A kinetic clutch governs religation by type IB topoisomerases and determines camptothecin sensitivity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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
40 citing papers in PubMed.
- Type II topoisomerase substrate geometry revealed through combined experiment and computation.bioRxiv : the preprint server for biology · 2026Article
- Networked salt-bridges mediate magnesium-dependent conformational dynamics and functional regulation in type IA topoisomerases.Nature communications · 2026Article
- Hybrid thiazolyl-benzylidene-phenol metal complexes as novel chemotherapeutic agents with anti-topoisomerase I activity in human breast carcinoma: synthesis,RSC advances · 2025Article
- The low endoribonuclease activity and lack of rNMP preference of human mitochondrial topoisomerase 1 protect against ribonucleotide-dependent deletions.Nucleic acids research · 2025Article
- Nuclear TOP1MT Confers Cisplatin Resistance via Pseudogene in HNSCC.Journal of dental research · 2024Article
- Genome-wide Mapping of Topoisomerase Binding Sites Suggests Topoisomerase 3α (TOP3A) as a Reader of Transcription-Replication Conflicts (TRC).bioRxiv : the preprint server for biology · 2024Article
- Article
- TOP1 CAD-seq: A protocol to map catalytically engaged topoisomerase 1 in human cells.STAR protocols · 2022Article
- Human topoisomerases and their roles in genome stability and organization.Nature reviews. Molecular cell biology · 2022Review
- Topoisomerase I (TOP1) dynamics: conformational transition from open to closed states.Nature communications · 2022Article
- A comprehensive pan-cancer analysis of the expression characteristics, prognostic value, and immune characteristics ofFrontiers in genetics · 2022Article
- Distant residues modulate conformational opening in SARS-CoV-2 spike protein.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Three different mutations in the DNA topoisomerase 1B in Leishmania infantum contribute to resistance to antitumor drug topotecan.Parasites & vectors · 2021Article
- Topoisomerase I activity and sensitivity to camptothecin in breast cancer-derived cells: a comparative study.BMC cancer · 2019Article
- Kinetic Study of DNA Topoisomerases by Supercoiling-Dependent Fluorescence Quenching.ACS omega · 2019Article
- The mitochondrial type IB topoisomerase drives mitochondrial translation and carcinogenesis.Nature communications · 2019Article
- Topoisomerase II Poisons for Glioblastoma; Existing Challenges and Opportunities to Personalize Therapy.Frontiers in neurology · 2018Review
- Distribution bias and biochemical characterization of TOP1MT single nucleotide variants.Scientific reports · 2017Article
- Mitochondrial protein-linked DNA breaks perturb mitochondrial gene transcription and trigger free radical-induced DNA damage.Science advances · 2017Article
- The dynamic interplay between DNA topoisomerases and DNA topology.Biophysical reviews · 2016Review
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.
Funding
Abstract
Type IB topoisomerases (Top1Bs) relax excessive DNA supercoiling associated with replication and transcription by catalyzing a transient nick in one strand to permit controlled rotation of the DNA about the intact strand. The natural compound camptothecin (CPT) and the cancer chemotherapeutics derived from it, irinotecan and topotecan, are highly specific inhibitors of human nuclear Top1B (nTop1). Previous work on vaccinia Top1B led to an elegant model that describes a straightforward dependence of rotation and religation on the torque caused by supercoiling. Here, we used a single-molecule DNA supercoil relaxation assay to measure the torque dependence of nTop1 and its inhibition by CPT. For comparison, we also examined mitochondrial Top1B and an N-terminal deletion mutant of nTop1. Despite substantial sequence homology in their core domains, nTop1 and mitochondrial Top1B exhibit dramatic differences in sensitivity to torque and CPT, with the N-terminal deletion mutant of nTop1 showing intermediate characteristics. In particular, nTop1 displays nearly torque-independent religation probability, distinguishing it from other Top1B enzymes studied to date. Kinetic modeling reveals a hitherto unobserved torque-independent transition linking the DNA rotation and religation phases of the enzymatic cycle. The parameters of this transition determine the torque sensitivity of religation and the efficiency of CPT binding. This "kinetic clutch" mechanism explains the molecular basis of CPT sensitivity and more generally provides a framework with which to interpret Top1B activity and inhibition.
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.