ArticleThe Journal of biological chemistry2013
The structural location of DNA lesions in nucleosome core particles determines accessibility by base excision repair enzymes.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 94 citations in OpenAlex.
- CRISPR-mediated gap-based replacement enables site-specific DNA lesion insertion into long DNA and nucleosomes.Nucleic acids research · 2026Article
- Molecular basis of nick ligation in the nucleosome by DNA Ligase IIIα.Nature communications · 2026Article
- Navigating the base excision repair pathway in chromatin-focus on oxidative DNA damage.Nucleic acids research · 2026Review
- Structural basis of end processing in the nucleosome by polynucleotide kinase phosphatase.bioRxiv : the preprint server for biology · 2026Article
- Base excision repair in chromatin: A tug-of-war for DNA damage.DNA repair · 2025Review
- Mechanisms underlying low mutation rates in mammalian oocytes and preimplantation embryos.Nucleic acids research · 2025Review
- A Method for Constructing Nucleosome Arrays with Spatially Defined Histone PTMs and DNA Damage.Angewandte Chemie (International ed. in English) · 2025Article
- Initiation of base excision repair is modulated by nucleosome occupancy modifying sequences.DNA repair · 2025Article
- Mechanisms of DNA Damage Recognition by UDG and PARP1 in the Nucleosome.Biomolecules · 2025Article
- Structural basis of gap-filling DNA synthesis in the nucleosome by DNA Polymerase β.Nature communications · 2025Article
- CHD6 has poly(ADP-ribose)- and DNA-binding domains and regulates PARP1/2-trapping inhibitor sensitivity via abasic site repair.Nature communications · 2025Article
- Article
- Structural basis for human OGG1 processing 8-oxodGuo within nucleosome core particles.Nature communications · 2024Article
- DNA Repair in Nucleosomes: Insights from Histone Modifications and Mutants.International journal of molecular sciences · 2024Review
- New Discoveries on Protein Recruitment and Regulation during the Early Stages of the DNA Damage Response Pathways.International journal of molecular sciences · 2024Review
- Redox-Based Defect Detection in Packed DNA: Insights from Hybrid Quantum Mechanical/Molecular Mechanics Molecular Dynamics Simulations.Journal of chemical theory and computation · 2023Article
- Ionic strength modulates excision of uracil by SMUG1 from nucleosome core particles.DNA repair · 2023Article
- Generation of Recombinant Nucleosomes Containing Site-Specific DNA Damage.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Structural basis for APE1 processing DNA damage in the nucleosome.Nature communications · 2022Article
- Preparation of Nucleosome Core Particles Complexed with DNA Repair Factors for Cryo-Electron Microscopy Structural Determination.Journal of visualized experiments : JoVE · 2022Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundBase excision repair is hindered by nucleosomes.
resultsOutwardly oriented uracils near the nucleosome center are efficiently cleaved; however, polymerase β is strongly inhibited at these sites.
conclusionThe histone octamer presents different levels of constraints on BER, dependent on the structural requirements for enzyme activity. SIGNIFICANCE: Chromatin remodeling is necessary to prevent accumulation of aborted intermediates in nucleosomes. Packaging of DNA into chromatin affects accessibility of DNA regulatory factors involved in transcription, replication, and repair. Evidence suggests that even in the nucleosome core particle (NCP), accessibility to damaged DNA is hindered by the presence of the histone octamer. Base excision repair is the major pathway in mammalian cells responsible for correcting a large number of chemically modified bases. We have measured the repair of site-specific uracil and single nucleotide gaps along the surface of the NCP. Our results indicate that removal of DNA lesions is greatly dependent on their rotational and translational positioning in NCPs. Significantly, the rate of uracil removal with outwardly oriented DNA backbones is 2-10-fold higher than those with inwardly oriented backbones. In general, uracils with inwardly oriented backbones farther away from the dyad center of the NCP are more accessible than those near the dyad. The translational positioning of outwardly oriented gaps is the key factor driving gap filling activity. An outwardly oriented gap near the DNA ends exhibits a 3-fold increase in gap filling activity as compared with one near the dyad with the same rotational orientation. Near the dyad, uracil DNA glycosylase/APE1 removes an outwardly oriented uracil efficiently; however, polymerase β activity is significantly inhibited at this site. These data suggest that the hindrance presented by the location of a DNA lesion is dependent on the structural requirements for enzyme catalysis. Therefore, remodeling at DNA damage sites in NCPs is critical for preventing accumulation of aborted intermediates and ensuring completion of base excision repair.
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