ArticleDNA repair2017
Structure-activity relationships among DNA ligase inhibitors: Characterization of a selective uncompetitive DNA ligase I inhibitor.
Article in DNA repair, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
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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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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.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- PARP1-mediated 5' flap dynamics facilitate Okazaki fragment maturation.bioRxiv : the preprint server for biology · 2026Article
- Mitotic microhomology-mediated break-induced replication promotes chromoanasynthesis.Nature communications · 2026Article
- Development of a Synthetic Lethality-Based Combination Therapy Using LIG1 and PARP Inhibitors for Prostate Cancer.Cancer science · 2025Article
- Impact of DNA ligase inhibition on the nick sealing of polβ nucleotide insertion products at the downstream steps of base excision repair pathway.Mutagenesis · 2024Article
- Redundant but essential functions of PARP1 and PARP2 in DNA ligase I-independent DNA replication.Nucleic acids research · 2024Article
- Base Excision Repair: Mechanisms and Impact in Biology, Disease, and Medicine.International journal of molecular sciences · 2023Review
- Unchanged PCNA and DNMT1 dynamics during replication in DNA ligase I-deficient cells but abnormal chromatin levels of non-replicative histone H1.Scientific reports · 2023Article
- Integrative analysis and prediction of human R-loop binding proteins.G3 (Bethesda, Md.) · 2022Article
- Integrative analysis of therapy resistance and transcriptomic profiling data in glioblastoma cells identifies sensitization vulnerabilities for combined modality radiochemotherapy.Radiation oncology (London, England) · 2022Article
- DNA damage repair: historical perspectives, mechanistic pathways and clinical translation for targeted cancer therapy.Signal transduction and targeted therapy · 2021Review
- DNA ligase I variants fail in the ligation of mutagenic repair intermediates with mismatches and oxidative DNA damage.Mutagenesis · 2020Article
- Base excision repair and its implications to cancer therapy.Essays in biochemistry · 2020Review
- Pol μ ribonucleotide insertion opposite 8-oxodG facilitates the ligation of premutagenic DNA repair intermediate.Scientific reports · 2020Article
- Development of an effective fluorescence probe for discovery of aminopeptidase inhibitors to suppress biofilm formation.The Journal of antibiotics · 2019Article
- Interplay between DNA Polymerases and DNA Ligases: Influence on Substrate Channeling and the Fidelity of DNA Ligation.Journal of molecular biology · 2019Review
- DNA Ligase 1 is an essential mediator of sister chromatid telomere fusions in G2 cell cycle phase.Nucleic acids research · 2019Article
- The oncogenic RNA-binding protein SRSF1 regulates LIG1 in non-small cell lung cancer.Laboratory investigation; a journal of technical methods and pathology · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 5 institutions in 1 country.
Funding
Abstract
In human cells, there are three genes that encode DNA ligase polypeptides with distinct but overlapping functions. Previously small molecule inhibitors of human DNA ligases were identified using a structure-based approach. Three of these inhibitors, L82, a DNA ligase I (LigI)-selective inhibitor, and L67, an inhibitor of LigI and DNA ligases III (LigIII), and L189, an inhibitor of all three human DNA ligases, have related structures that are composed of two 6-member aromatic rings separated by different linkers. Here we have performed a structure-activity analysis to identify determinants of activity and selectivity. The majority of the LigI-selective inhibitors had a pyridazine ring whereas the LigI/III- and LigIII-selective inhibitors did not. In addition, the aromatic rings in LigI-selective inhibitors had either arylhydrazone or acylhydrazone, but not vinyl linkers. Among the LigI-selective inhibitors, L82-G17 exhibited increased activity against and selectivity for LigI compared with L82. Notably. L82-G17 is an uncompetitive inhibitor of the third step of the ligation reaction, phosphodiester bond formation. Cells expressing LigI were more sensitive to L82-G17 than isogenic LIG1 null cells. Furthermore, cells lacking nuclear LigIIIα, which can substitute for LigI in DNA replication, were also more sensitive to L82-G17 than isogenic parental cells. Together, our results demonstrate that L82-G17 is a LigI-selective inhibitor with utility as a probe of the catalytic activity and cellular functions of LigI and provide a framework for the future design of DNA ligase inhibitors.
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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.