ArticleBiochemistry2020
Probing the Conformational Changes Associated with DNA Binding to PARP1.
Article in Biochemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- The BRCT domain enhances DNA binding and catalytic efficiency of fungal PARPs.Nature communications · 2026Article
- PARP4 ADP-ribosylates PIDD1 to complete a phospho/SUMO/PAR-ylation cascade that orchestrates PIDDosome assembly.Science advances · 2026Article
- The dynamics and regulation of PARP1 and PARP2 in response to DNA damage and during replication.DNA repair · 2024Review
- Slow Dissociation from the PARP1-HPF1 Complex Drives Inhibitor Potency.Biochemistry · 2023Article
- Dynamics of endogenous PARP1 and PARP2 during DNA damage revealed by live-cell single-molecule imaging.iScience · 2023Article
- Article
- Deciphering the functional mechanism of zinc ions of PARP1 binding with single strand breaks and double strand breaks.RSC advances · 2022Article
- Inhibitors of PARP: Number crunching and structure gazing.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The potential of PARP inhibitors in targeted cancer therapy and immunotherapy.Frontiers in molecular biosciences · 2022Review
- The BRCT domain of PARP1 binds intact DNA and mediates intrastrand transfer.Molecular cell · 2021Article
- Role of PARP in TNBC: Mechanism of Inhibition, Clinical Applications, and Resistance.Biomedicines · 2021Review
- PARP Power: A Structural Perspective on PARP1, PARP2, and PARP3 in DNA Damage Repair and Nucleosome Remodelling.International journal of molecular sciences · 2021Review
- HPF1 and nucleosomes mediate a dramatic switch in activity of PARP1 from polymerase to hydrolase.eLife · 2021Article
- The contribution of PARP1, PARP2 and poly(ADP-ribosyl)ation to base excision repair in the nucleosomal context.Scientific reports · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Poly(ADP-ribose) polymerase 1 (PARP1) is an important first responder in the mechanism of DNA repair in eukaryotic cells. It is also a validated drug target, with four different PARP inhibitors (PARPi) approved for the treatment of BRCA-negative cancers. Despite past efforts, many aspects of PARPi are poorly understood, in particular their ability to trap PARP1 on chromatin and the relationships between their potencies, cellular toxicities, and trapping efficiencies. Because PARP trapping is widely believed to originate in allosteric coupling between DNA binding and the catalytic site, we further investigated the binding properties of PARP1 to a model for DNA with a double-strand break in the presence and absence of PARPi. Specifically, we have used sequential mixing stopped-flow spectroscopy to identify a slow conformational change that follows rapid DNA binding. Using a range of DNA concentrations and different mutants of PARP1 we demonstrate that this conformational change is one of the steps of the "monkey bar mechanism" that promotes DNA-dependent dissociation of DNA. This conformational change also corresponds to the previously identified conformational change associated with DNA-dependent activation of PARP1. Despite linking the conformational change associated with DNA binding and release to DNA activation, we find no evidence for PARPi perturbing this allosteric coupling.
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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.