ArticleNucleic acids research2021
An atypical BRCT-BRCT interaction with the XRCC1 scaffold protein compacts human DNA Ligase IIIα within a flexible DNA repair complex.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Molecular basis of nick ligation in the nucleosome by DNA Ligase IIIα.Nature communications · 2026Article
- Interplay Between Poly(ADP-ribosyl)ation and Specific Inner Cellular Events That Suggest Combination Strategies for Overcoming PARP Inhibitor Resistance.Pharmaceutics · 2026Review
- The zinc finger of DNA ligase 3α binds to nucleosomes via an arginine anchor.Nature communications · 2025Article
- XRCC1 mediates PARP1- and PAR-dependent recruitment of PARP2 to DNA damage sites.Nucleic acids research · 2025Article
- DNA Repair Protein XRCC1 Stimulates Activity of DNA Polymerase λ under Conditions of Microphase Separation.International journal of molecular sciences · 2024Article
- Mammalian DNA ligases; roles in maintaining genome integrity.Journal of molecular biology · 2024Review
- Novobiocin blocks nucleic acid binding to Polθ and inhibits stimulation of its ATPase activity.Nucleic acids research · 2023Article
- The Role of Poly(ADP-ribose) Polymerase 1 in Nuclear and Mitochondrial Base Excision Repair.Biomolecules · 2023Review
- The function and regulation of ADP-ribosylation in the DNA damage response.Biochemical Society transactions · 2023Article
- BRCT Domains: Structure, Functions, and Implications in Disease-New Therapeutic Targets for Innovative Drug Discovery against Infections.Pharmaceutics · 2023Review
- NBS1 binds directly to TOPBP1 via disparate interactions between the NBS1 BRCT1 domain and the TOPBP1 BRCT1 and BRCT2 domains.DNA repair · 2023Article
- Combining small angle X-ray scattering (SAXS) with protein structure predictions to characterize conformations in solution.Methods in enzymology · 2023Article
- Article
- Universally Accessible Structural Data on Macromolecular Conformation, Assembly, and Dynamics by Small Angle X-Ray Scattering for DNA Repair Insights.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Purification and Characterization of Human DNA Ligase IIIα Complexes After Expression in Insect Cells.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Article
- X-ray scattering reveals disordered linkers and dynamic interfaces in complexes and mechanisms for DNA double-strand break repair impacting cell and cancer biology.Protein science : a publication of the Protein Society · 2021Review
- Targeting protein-protein interactions in the DNA damage response pathways for cancer chemotherapy.RSC chemical biology · 2021Review
- Function and Molecular Mechanism of the DNA Damage Response in Immunity and Cancer Immunotherapy.Frontiers in immunology · 2021Review
- An efficient chemical screening method for structure-based inhibitors to nucleic acid enzymes targeting the DNA repair-replication interface and SARS CoV-2.Methods in enzymology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
The XRCC1-DNA ligase IIIα complex (XL) is critical for DNA single-strand break repair, a key target for PARP inhibitors in cancer cells deficient in homologous recombination. Here, we combined biophysical approaches to gain insights into the shape and conformational flexibility of the XL as well as XRCC1 and DNA ligase IIIα (LigIIIα) alone. Structurally-guided mutational analyses based on the crystal structure of the human BRCT-BRCT heterodimer identified the network of salt bridges that together with the N-terminal extension of the XRCC1 C-terminal BRCT domain constitute the XL molecular interface. Coupling size exclusion chromatography with small angle X-ray scattering and multiangle light scattering (SEC-SAXS-MALS), we determined that the XL is more compact than either XRCC1 or LigIIIα, both of which form transient homodimers and are highly disordered. The reduced disorder and flexibility allowed us to build models of XL particles visualized by negative stain electron microscopy that predict close spatial organization between the LigIIIα catalytic core and both BRCT domains of XRCC1. Together our results identify an atypical BRCT-BRCT interaction as the stable nucleating core of the XL that links the flexible nick sensing and catalytic domains of LigIIIα to other protein partners of the flexible XRCC1 scaffold.
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Registered trials
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