ArticleJournal of nucleic acids2011
The stability of a model substrate for topoisomerase 1-mediated DNA religation depends on the presence of mismatched base pairs.
Article in Journal of nucleic acids, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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Who cites it
10 citing papers in PubMed.
- Entrapment of DNA topoisomerase-DNA complexes by nucleotide/nucleoside analogs.Cancer drug resistance (Alhambra, Calif.) · 2019Article
- Using correlated motions to determine sufficient sampling times for molecular dynamics.Physical review. E · 2018Article
- Visualizing correlated motion with HDBSCAN clustering.Protein science : a publication of the Protein Society · 2018Article
- All-Atom MD Predicts Magnesium-Induced Hairpin in Chemically Perturbed RNA Analog of F10 Therapeutic.The journal of physical chemistry. B · 2017Article
- All-atom MD indicates ion-dependent behavior of therapeutic DNA polymer.Physical chemistry chemical physics : PCCP · 2017Article
- MutSFrontiers in physics · 2017Article
- Uncovering Large-Scale Conformational Change in Molecular Dynamics without Prior Knowledge.Journal of chemical theory and computation · 2016Article
- All-Atom Molecular Dynamics Reveals Mechanism of Zinc Complexation with Therapeutic F10.The journal of physical chemistry. B · 2016Article
- Replication-dependent irreversible topoisomerase 1 poisoning is responsible for FdUMP[10] anti-leukemic activity.Experimental hematology · 2013Article
- Cooperative stabilization of Zn(2+):DNA complexes through netropsin binding in the minor groove of FdU-substituted DNA.Journal of biomolecular structure & dynamics · 2013Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Topoisomerase 1 (Top1) enzymes regulate DNA superhelicity by forming covalent cleavage complexes that undergo controlled rotation. Substitution of nucleoside analogs at the +1 position of the DNA duplex relative to the Top1 cleavage site inhibits DNA religation. The reduced efficiency for Top1-mediated religation contributes to the anticancer activity of widely used anticancer drugs including fluoropyrimidines and gemcitabine. In the present study, we report that mismatched base pairs at the +1 position destabilize the duplex DNA components for a model Top1 cleavage complex formation even though one duplex component does not directly include a mismatched base pair. Molecular dynamics simulations reveal G-dU and G-FdU mismatched base pairs, but not a G-T mismatched base pair, increase flexibility at the Top1 cleavage site, and affect coupling between the regions required for the religation reaction to occur. These results demonstrate that substitution of dT analogs into the +1 position of the non-scissile strand alters the stability and flexibility of DNA contributing to the reduced efficiency for Top1-mediated DNA religation. These effects are inherent in the DNA duplex and do not require formation of the Top1:DNA complex. These results provide a biophysical rationale for the inhibition of Top1-mediated DNA religation by nucleotide analog substitution.
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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.